Targeted co-delivery of antigens and adjuvants to dendritic cells (DCs) represents an effective strategy to remodel the immunosuppressive tumor microenvironment and enhance the immune response of cancer vaccines. Meanwhile, activation of the STING pathway can trigger significant type I interferon expression and promote DC maturation. In this study, a novel delivery system CPTS was constructed by covalently modifying the STING agonist DMXAA onto polymer backbone to achieve precise co-delivery of tumor-associated antigen OVA and STING adjuvant. In vitro experiments demonstrated that CPTS significantly enhanced the uptake of antigens by DCs. To further improve biocompatibility and Lymph nodes targeting capability, outer membrane vesicles (OMVs), a natural biomembrane material, were employed to encapsulate the CPTS/OVA complex, forming a nanocarrier system CPTS/OVA@OMVs. The inherent immunostimulatory properties of OMVs also contributed to enhanced DC maturation and antigen presentation. The results revealed that dual activation by the STING pathway and OMVs stimulation induced high levels of type I interferon expression in bone marrow-derived dendritic cells (BMDCs), significantly enhancing their maturation and antigen cross-presentation capability. In vivo studies further confirmed that the CPTS/OVA@OMVs system effectively promoted the proliferation and differentiation of CTLs, facilitated CTL infiltration into the tumor microenvironment, and significantly inhibited tumor growth. This study successfully engineered a highly efficient and low-toxicity modular vaccine delivery platform by strategically integrating the advantages of synthetic polymers with the natural biomaterials, which provide synergistic immunostimulation and targeted delivery platform, offering a promising and broadly applicable strategy for cancer vaccines.

As mRNA vaccines continue to gain widespread attention, the development of lipid nanoparticles (LNPs), as the preferred platform for mRNA delivery, has become a key focus of research. 1,4,7,10-Tetraazacyclododecane (cyclen), with its excellent protonation capability and ease of modification, has emerged as a promising candidate for the ionizable head group of lipid materials. In this study, a series of cyclen-based lipidoids with different linkages and hydrophobic tails was designed and conveniently synthesized. Structure-activity relationship studies were performed to screen out the carriers capable of efficient mRNA delivery and with potential for tumor therapeutic applications. In vivo biodistribution experiments in mice revealed that the lipidoid OEs-K, containing both hydroxyl and ester groups in its linkage, exhibited high mRNA delivery efficiency and lymph node-targeting properties. Using a subcutaneous EG.7-OVA tumor model in mice, the delivery of tumor antigen OVA mRNA using the lipidoid material was evaluated for its antitumor immunotherapeutic potential. Results demonstrated that LNPs formulated with OEs-K promoted dendritic cell uptake in lymph nodes, effectively activated immune responses, and inhibited tumor growth. Hematological and histopathological evaluations indicated no significant toxicity to the body. This study provides insights into the design and development of carrier materials for mRNA vaccines.

Background: Intravenous vitamin C (IVC, ascorbate [Asc]) and alpha-lipoic acid (ALA) are frequently coadministered in integrative oncology clinics, with limited understanding of combination effects or drug-drug interactions. As high-dose IVC has anticancer activity through peroxide (H2O2), it is hypothesized that IV ALA, a thiol antioxidant, might have untoward effects when combined with IVC. Methods: In vitro combination index (CI) was investigated in 6 types of human cancer cells, using clinically relevant concentrations of Asc (0.625-20 mM) and ALA (0.25, 0.5, and 1 mM) evaluated by nonconstant ratio metrics. Cellular H2O2 was measured using HeLa cells expressing a fluorescent probe HyPer. Mouse xenografts of the metastatic breast cancer MDA-MB-231 were treated with intraperitoneal injections of ALA (10, 20, and 50 mg/kg) and Asc (0.2, 0.5, and 4 g/kg) at various dose levels. Results: Cancer cell lines were sensitive to Asc treatment but not to ALA. There is no evidence ALA becomes a prooxidant at higher doses. The CIs showed a mixture of synergistic and antagonistic effects with different ALA and Asc combination ratios, with a “U” shape response to Asc concentrations. The ALA concentrations did not influence the CIs or cellular H2O2 formation. Adding ALA to Asc dampened the increase of H2O2. Toxicity was observed in mice receiving prolonged treatment of ALA at all doses. The Asc at all doses was nontoxic. The combination of ALA and Asc increased toxicity. The ALA at all doses did not inhibit tumor growth. The Asc at 4 g/kg inhibited tumor growth. Adding ALA 50 mg/kg to Asc 4 g/kg did not enhance the effect, but lower doses of ALA (10 or 20 mg/kg) dampened the inhibitory effect of Asc. Conclusions: These data do not support the concurrent or relative concurrent use of high-dose intravenous ALA with prooxidative high-dose IVC in clinical oncology care with potentially increased toxicity.

Hepatocellular carcinoma (HCC) is one of the most aggressive and dismal cancers globally. Emerging evidence has established that mTOR and Hippo pathways are oncogenic drivers of HCC. However, the prognostic value of these pathways in HCC remains unclear. In this study, we aimed to develop a gene signature utilizing the mTOR/Hippo genes for HCC prognostication. A multiple stage strategy was employed to screen, and a 12-gene signature based on mTOR/Hippo pathways was constructed to predict the prognosis of HCC patients. The risk scores calculated by the signature were inversely correlated with patient prognosis. Validation of the signature in independent cohort confirmed its predictive power. Further analysis revealed molecular differences between high and low-risk groups at genomic, transcriptomic, and protein-interactive levels. Moreover, immune infiltration analysis revealed an immunosuppressive state in the high-risk group. Finally, the gene signature could predict the sensitivity to current chemotherapeutic drugs. This study demonstrated that combinatorial mTOR/Hippo gene signature was a robust and independent prognostic tool for survival prediction of HCC. Our findings not only provide novel insights for the molecular understandings of mTOR/Hippo pathways in HCC, but also have important clinical implications for guiding therapeutic strategies.

Two photostable carbon dots were simply prepared and separated with entirely different organelle-targeting abilities.

Based on the characteristics and learning situations of the cell biology course in medical colleges,traditional classroom teaching is combined with cloud classroom-assisted teaching for the 2020 students（experimental group）,while the 2019 students（control group） receive traditional classroom teaching. After the end of the course,the final exam scores of the two groups were statistically analyzed,and the experimental group performed better than the control group. The results of the questionnaire survey show that the experimental group recognizes the blended teaching in promoting self-learning,stimulating learning potential,improving abilities,and broadening horizons. The blended teaching design of cloud classroom combined with traditional classroom can enhance students’ initiative in learning,and is beneficial to improving the quality of teaching cell biology in medical colleges.

BACKGROUND:Related to the SARS-CoV-2 pandemic leading to COVID-19 illness, patients with cancer comorbidity are known to have a higher risk of developing severe viral-related events, including death. To date, there are few treatments with proven efficacy for COVID-19. Vitamin C administered intravenously (IVC) has been extensively investigated in cancer treatment with a known safety profile and has been proposed to play a role in managing COVID-19. IVC was used to treat COVID-19 patients in hospitals in China, USA, and Europe with reported benefits. We report here unexpected beneficial results from the use of IVC in two severely ill oncology patients with documented COVID-19 lung disease.CASE REPORT:two oncology patients were diagnosed with SARS-CoV-2 infection. Prior to receiving IVC, lung infiltrates and systemic inflammation in both patients were progressing despite multiple anti-viral, antibiotic, and anti-inflammatory treatments with intensive supportive care. Both patients subsequently received 12 g of IVC delivered intravenously over 30 min, given 2 times daily for 7 days. Serial SARS-CoV-2 nucleic acid tests showed that the viral load was negative only after the 7-day IVC treatment. In both patients after receiving IVC infusions, imaging by chest CT or X-ray showed improving lung infiltrates. There were reductions in systematic inflammation by high-sensitivity C-reactive protein (hsCRP), and Interleukin-6 (IL-6) testing. No adverse events were observed related to IVC treatment.CONCLUSION:the use of high-dose IVC demonstrated unexpected clinical benefits in treating COVID-19 in two cancer patients presenting with complicated severe comorbidities where an unfavorable prognosis was anticipated.

You have accessJournal of UrologyCME1 May 2022LBA01-09 INTERIM ANALYSIS NCT04046094: IV VITAMIN C WITH CHEMOTHERAPY FOR CISPLATIN INELIGIBLE BLADDER CANCER PATIENTS (CI-MIBC) John Taylor, Rahul Parikh, Qi Chen, Benjamin Woolbright, Ping Chen, Elizabeth Wulff-Burchfield, Jeff Holzbeierlein, Jane Ledesma, Roy Jensen, and Jeanne Drisko John TaylorJohn Taylor More articles by this author , Rahul ParikhRahul Parikh More articles by this author , Qi ChenQi Chen More articles by this author , Benjamin WoolbrightBenjamin Woolbright More articles by this author , Ping ChenPing Chen More articles by this author , Elizabeth Wulff-BurchfieldElizabeth Wulff-Burchfield More articles by this author , Jeff HolzbeierleinJeff Holzbeierlein More articles by this author , Jane LedesmaJane Ledesma More articles by this author , Roy JensenRoy Jensen More articles by this author , and Jeanne DriskoJeanne Drisko More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002669.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ∼40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usually proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy in other models. This single-arm, Simon 2-stage, window of opportunity trial included IVC with single cycle GCa to evaluate pathologic downstaging. We report on the interim first stage analysis of 12 patients. METHODS: Patients with newly diagnosed CI-MIBC were enrolled and received single cycle GCa and IVC titrated to peak plasma concentration of 350 to 400 mg/dL (∼20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. The primary outcome is pathological stage at cystectomy. Patients are then followed per NCCN guidelines with standard of care bloodwork, physical exam and imaging studies until progression and/or death. QOL is being evaluated by Functional Assessment of Cancer Therapy-Bladder (FACT-Bl). RESULTS: All 12 patients completed GCa/IVC with 11 having had a cystectomy and 1 pending surgery. Pathological downstaging (yp 36% rate of downstaging. Of those with a pathological response, 75% achieved a CR. Continuation criteria has been met for stage 2. FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion. Source of Funding: NCATS/CTSA KU Frontiers: KU CTSI UL1TR002366, NCI Cancer Center Support Grant P30 CA168524 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1039 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Taylor More articles by this author Rahul Parikh More articles by this author Qi Chen More articles by this author Benjamin Woolbright More articles by this author Ping Chen More articles by this author Elizabeth Wulff-Burchfield More articles by this author Jeff Holzbeierlein More articles by this author Jane Ledesma More articles by this author Roy Jensen More articles by this author Jeanne Drisko More articles by this author Expand All Advertisement PDF downloadLoading ...

Ovarian cancer has an enrichment of cancer stem cells (CSCs) which contribute to the treatment resistant tumor’s high rate of recurrence and metastasis. Here we investigated 2 plant extracts from the medicinal plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) each for their activities against ovarian CSCs. Both Pao and Rau inhibited overall proliferation of human ovarian cancer cell lines with IC 50 ranging from 210 to 420 μg/mL and had limited cytotoxicity to normal epithelial cells. Ovarian CSC population was examined using cell surface markers and tumor spheroid formation assays. The results showed that both Pao and Rau treatment significantly reduced the ovarian CSC population. Pao and Rau had similar activities in inhibiting ovarian CSCs, with IC 50 s of ~120 μg/mL for 24 hours treatment, and ~50 μg/mL for long-term tumor spheroid formation. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. Taken together, data here showed that Pao and Rau both inhibited ovarian cancer stem cells, probably in preference to the bulk of tumor cells. Further mechanistic studies and in vivo investigation validating these findings are warranted, given that inhibition of cancer stem cells holds the promise of comprehensively inhibiting cancer metastasis, drug resistance and recurrence. Keywords ovarian cancer , cancer stem cells , Pao Pereira , , , medicinal plant , natural product

Pancreatic cancer is a devastating disease with a dismal prognosis and poor treatment outcomes. Searching for new agents for pancreatic cancer treatment is of great significance. We previously identified a novel activity of compound C150 to inhibit pancreatic cancer epithelial-to-mesenchymal transition (EMT). Here, we further revealed its mechanism of action. C150 induced ER stress in pancreatic cancer cells and subsequently increased proteasome activity by enhancing proteasome assembly, which subsequently enhanced the degradation of critical EMT transcription factors (EMT-TFs). In addition, as cellular responses to ER stress, autophagy was elevated, and general protein synthesis was inhibited in pancreatic cancer cells. Besides EMT inhibition, the C150-induced ER stress resulted in G2/M cell cycle arrest, which halted cell proliferation and led to cellular senescence. In an orthotopic syngeneic mouse model, an oral dose of C150 at 150 mg/kg 3× weekly significantly increased survival of mice bearing pancreatic tumors, and reduced tumor growth and ascites occurrence. These results suggested that compound C150 holds promises in comprehensively inhibiting pancreatic cancer progression.

Ovarian cancer has an enrichment of cancer stem cells (CSCs) which contribute to the treatment resistant tumor's high rate of recurrence and metastasis. Here we investigated 2 plant extracts from the medicinal plants Pao Pereira (Pao) and Rauwolfia vomitoria (Rau) each for their activities against ovarian CSCs. Both Pao and Rau inhibited overall proliferation of human ovarian cancer cell lines with IC50 ranging from 210 to 420 μg/mL and had limited cytotoxicity to normal epithelial cells. Ovarian CSC population was examined using cell surface markers and tumor spheroid formation assays. The results showed that both Pao and Rau treatment significantly reduced the ovarian CSC population. Pao and Rau had similar activities in inhibiting ovarian CSCs, with IC50s of ~120 μg/mL for 24 hours treatment, and ~50 μg/mL for long-term tumor spheroid formation. Nuclear β-catenin levels were decreased, suggesting suppression of Wnt/β-catenin signaling pathway. Taken together, data here showed that Pao and Rau both inhibited ovarian cancer stem cells, probably in preference to the bulk of tumor cells. Further mechanistic studies and in vivo investigation validating these findings are warranted, given that inhibition of cancer stem cells holds the promise of comprehensively inhibiting cancer metastasis, drug resistance and recurrence.

e16540 Background: Neo-adjuvant cisplatin-based chemotherapy (NAC) is considered standard of care for patients with locally advanced disease. However, ̃40% of patients are cisplatin ineligible (CI) due to renal insufficiency, hearing loss or poor performance status. Gemcitabine and carboplatin (GCa) has limited success in this setting. Patients usually proceed directly to cystectomy without realizing the potential survival benefit afforded by NAC. Intravenous ascorbate (vitamin C) administration (IVC) has been shown to improve the efficacy of carboplatin and gemcitabine-based therapy in other models. This single-arm, Simon 2-stage, window of opportunity trial included IVC with single cycle GCa to evaluate pathologic downstaging. We report on the interim first stage analysis of 12 patients. Methods: Patients with newly diagnosed CI-MIBC were enrolled and received single cycle GCa and IVC titrated to peak plasma concentration of 350 to 400 mg/dL (̃20 mM) for 21 days followed by cystectomy at 4-6 weeks from initiation of treatment. The primary outcome is pathological stage at cystectomy. Patients are then followed per NCCN guidelines with standard of care bloodwork, physical exam and imaging studies until progression and/or death. QOL is being evaluated by Functional Assessment of Cancer Therapy-Bladder (FACT-Bl). Results: All 12 patients completed GCa/IVC with 11 having had a cystectomy and 1 pending surgery. Pathological downstaging (yp < T2) was noted in 4 patients with 3 CRs (ypT0N0Mx) and 1 with residual ypTisN0Mx only. Of note, 1 CR was seen in a patient with locally advanced plasmacytoid variant. Participants tolerated treatment well with minimal treatment related AE/SAEs. Conclusions: Interim analysis of GCa-IVC NAC shows good tolerability with > 36% rate of downstaging. Of those with a pathological response, 75% achieved a CR. Continuation criteria has been met for stage 2. FACT-BI analysis and clinical follow up is ongoing and will be reported at study completion. Clinical trial information: NCT04046094.

Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1–100 g. A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1–100 g; oncology participants received IVC infusions of 25–100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study. In both cohorts, IVC exhibited first-order kinetics at doses up to 75 g. At 100 g, maximum concentration (Cmax) plateaued in both groups, whereas area under the concentration–time curve (AUC) only plateaued in the healthy group. IVC was primarily excreted through urine. No saturation of clearance was observed; however, the mean 24-h total IVC excretion in urine for all doses was lower in oncology participants (89% of dose) than in healthy participants at 100 g (99%). No significant adverse events were observed; thus, maximum tolerated dose (MTD) was not reached. IVC followed first-order pharmacokinetics up to 75 g and at up to 100 g had complete renal clearance in 24 h. IVC up to 100 g elicited no adverse effects or significant physiological/biochemical changes and appears to be safe. These data can be used to rectify existing misinformation and to guide future clinical trials. ClinicalTrials.gov identifier number NCT01833351.

As a new-type of fluorescent material, carbon dots (CDs) are promising nanoscale reagents with the potential to integrate the functions of bio-imaging and gene/drug delivery. Most of the reported CDs for nucleic acid delivery only emitted short-wavelength (blue and green) fluorescence, making them unsuitable for in vivo application. Herein, a one-step solvothermal method was applied to prepare CDs with long wavelength emission from low molecular weight PEI and rhodamine dyes for both bio-imaging and gene delivery. The structure of the CDs was confirmed by several analytical methods including 1H NMR, FT-IR, TEM, and XPS. The results showed that the CDs possess excellent fluorescence properties, which enable their application in both in vitro and in vivo bio-imaging. Meanwhile, the CDs could also be used for the intracellular tracking of the gene delivery process. In vitro transfection results revealed that the CDs possessed high transfection efficiency, which was up to 162 times higher than that of the "golden standard" transfection reagent PEI 25 kDa. Besides, these CDs also exhibited better serum tolerance and lower cytotoxicity than PEI. A mechanistic study suggested that the CD/DNA complexes may release the nucleic acid cargo more effectively. This work provides a new method to prepare multi-functional CDs with non-viral gene delivery and long wavelength bio-imaging abilities.

Pancreatic cancer cell epithelial-to-mesenchymal transition (EMT) is an important contributor to cell invasion and tumor progression. Therefore, targeting EMT may be beneficial for pancreatic cancer treatment. The aim of the present study was to report on the inhibitory effect of the novel compound C150 on the EMT of pancreatic cancer cells. C150 inhibited cell proliferation in multiple pancreatic cancer cells with IC50 values of 1-2.5 μM, while in an non-cancerous pancreatic epithelial cell line hTERT-HPNE the IC50 value was >12.5 μM. C150 significantly inhibited pancreatic cancer cell migration and invasion, as demonstrated by 3-dimensional cell invasion, wound healing and Boyden chamber Transwell migration-invasion assays. Moreover, C150 treatment decreased MMP-2 gene expression in PANC-1 cells and reduced MMP-2 activity in gelatin zymography assay. In an orthotopic mouse model of pancreatic cancer, C150 significantly reduced tumor growth at the dose of 15 mg/kg by intraperitoneal injection three times per week. Furthermore, C150 enhanced protein degradation of Snail, an important EMT-promoting transcription factor, and decreased the expression of the mesenchymal marker N-cadherin, while it increased the expression of the epithelial markers zonula occludens-1 and claudin-1. The findings of the present study suggested that C150 is a novel EMT inhibitor that may be promising for inhibiting pancreatic cancer growth and metastasis.

: High‐dose intravenous vitamin C (IVC) is used in a variety of disorders and clinical trials (e.g. cancer, sepsis, burn, infection, fatigue, chelation). However, reliable pharmacokinetic (PK) data is limited and misinformation exists in clinical applications of vitamin C. Here we conducted a study in healthy volunteers and cancer patients to detail the PK of escalating doses of IVC from 1 to 100 g.

以邻氨基苯甲酰胺(5)为原料,依次经分子间环合、烷基化、氨解和分子内环合四步反应成功合成目标化合物3,4-二氢-2H-吡嗪并[2,1-b]喹唑啉-1,6-二酮(10),总收率为46.5％,其中,中间体(8)、(9)及目标化合物(10)均未见文献报道,其结构经1 H NMR和MS(ESI)确证,并采用MTT法初步评价目标化合物的体外抗肝癌活性.结果表明,3,4-二氢-2 H-吡嗪并[2,1-b]喹唑啉-1,6-二酮对SMMC-7721具有明显的抑制活性,优于阳性对照药舒尼替尼,可为进一步发现新型抗肝癌药物提供先导结构,也为该类衍生物的大量合成和结构改造提供参考方法.

Abstract Pancreatic cancer has poor prognosis and treatment outcomes due to its highly metastatic nature and resistance to current treatments. The RNA-binding protein (RBP) Hu-antigen R (HuR) is a central player in posttranscriptional regulation of cancer-related gene expression, and contributes to tumorigenesis, tumor growth, metastasis, and drug resistance. HuR has been suggested to regulate pancreatic cancer epithelial-to-mesenchymal transition (EMT), but the mechanism was not well understood. Here, we further elucidated the role HuR plays in pancreatic cancer cell EMT, and developed a novel inhibitor specifically interrupting HuR–RNA binding. The data showed that HuR binds to the 3′-UTR of the mRNA of the transcription factor Snail, resulting in stabilization of Snail mRNA and enhanced Snail protein expression, thus promoted EMT, metastasis, and formation of stem-like cancer cells (CSC) in pancreatic cancer cells. siRNA silencing or CRISPR/Cas9 gene deletion of HuR inhibited pancreatic cancer cell EMT, migration, invasion, and inhibited CSCs. HuR knockout cells had dampened tumorigenicity in immunocompromised mice. A novel compound KH-3 interrupted HuR–RNA binding, and KH-3 inhibited pancreatic cancer cell viability, EMT, migration/invasion in vitro. KH-3 showed HuR-dependent activity and inhibited HuR-positive tumor growth and metastasis in vivo.

ObjectiveEpithelial to Mesenchymal Transition (EMT) has been proposed to contribute importantly to metastasis, cancer stem cell (CSC) generation and drug resistance in many cancers. Targeting EMT may be promising to benefit cancer treatment. Our previous high throughput screening study has identified a potential EMT inhibitor (namely, C150) in pancreatic cancer cells. Here, we sought to investigate the activities of C150 in inhibiting pancreatic cancer cell invasion, migration and tumor growth in mice, as well as its mechanisms of EMT inhibition.MethodsCell viability was detected by MTT assay. Cell migration/invasion was detected by Boyden chamber trans‐well migration‐invasion assay, wound scratch assay and a 3‐dimension (3D) cell invasion assay. MMP zymography assay was used to indicate MMP inhibition. In vivo tumor growth was evaluated in an orthotopic mouse model of pancreatic cancer. EMT marker proteins were examined by western blot.ResultsC150 exhibited a well‐separated cytotoxicity between pancreatic cancer cells and non‐cancerous cells, with IC50 values of 1~2.5 μM in multiple pancreatic cancer cell lines and >25 μM in a noncancerous pancreatic epithelial cell line (hTERT‐HPNE). C150 was found to significantly inhibit PANC‐1 cell invasion in the 3‐dimension (3D) cell invasion model, the wound scratching assay and the Boyden Chamber trans‐well migration‐invasion assay. C150 treatment reduced the expressions of MMP‐2 and MMP‐9 in PANC‐1 cells, and inhibited MMP enzyme activity in zymography assay. In orthotopic pancreatic cancer mouse model, C150 significantly reduced tumor growth at the dose of 15 mg/kg, 3x weekly by IP injection. C150 decreased the mesenchymal markers of N‐cadherin and Snail while increased epithelial markers of ZO‐1 and Claudin‐1. Further studies revealed that C150 treatment significantly increased proteasome activity in the cell without changing the protein expression levels of proteasome subunits.ConclusionThe novel compound C150 inhibited pancreatic cancer cell migration, invasion, and in vivo tumor growth in mice. The compound increased cellular proteasome activity, which enhanced the protein degradation of Snail, resulting in EMT inhibition in the cell. The studies of more detailed mechanisms of C150 induced EMT inhibition and proteasome activation, as well as target identification are currently undergoing.Support or Funding InformationInstitutional Development Award (IDeA) of NIH and State of Kansas Grant # 8P30GM103495, KU Cancer Center Lied Basic Science Grant 2018