Targeted drug delivery with spatiotemporal control is critical for potent cancer therapy, yet inadequate subcellular delivery remains a major obstacle for DNA-targeted therapeutics due to multiple intracellular barriers. Herein, we report a photo-responsive polyprodrug supramolecular assembly to yield self-accelerated subcellular delivery of therapeutic cargoes for synergistic photochemotherapy against triple-negative breast cancer. The designed polyprodrug bears cleavable camptothecin pendants via thioketal-carbonate linkers and co-assembles with amphiphilic photosensitizers into ultrasmall supramolecular assembly, thereby affording sustained cargo release and enhanced singlet oxygen generation due to J-aggregate engineering of the photosensitizer within the assembly. Upon near-infrared light irradiation, the assembly elicits light-programmable drug release and lysosomal membrane disruption to facilitate rapid drug cytosolic translocation, followed by increased nuclear envelope permeability through lamin B1 downregulation and lipid peroxidation, thereby accelerating the permeation of cytosolic cargoes into the nucleus. Consequently, the self-accelerated intranuclear accumulation results in the eradication of intractable tumor through synergistic photochemotherapy. This study demonstrates a chemically programmed strategy for spatiotemporally-controlled subcellular delivery, providing a feasible avenue for highly effective cancer therapy.

Blood-brain barrier compromise represents a pivotal pathological mechanism in ischemic stroke, driving neurological deterioration. Netrin-5, an axon guidance protein family member, demonstrates regulatory potential for BBB integrity. Employing middle cerebral artery occlusion (MCAO) mice and oxygen-glucose deprivation/reperfusion (OGD/R) in human brain microvascular endothelial cells (HBMVECs), we found that Netrin-5 was significantly downregulated in the murine cortex post-MCAO and was also downregulated in HBMVECs upon OGD/R exposure. Adenoviral Netrin-5 delivery in MCAO mice attenuated cerebral infarction, improved functional outcomes, reduced edema, and preserved BBB integrity, evidenced by diminished Evans blue extravasation and albumin leakage. Furthermore, Netrin-5 restored tight junction protein ZO-1 expression and activated Wnt3a/β-catenin signaling. In HBMVECs, Netrin-5 overexpression counteracted OGD/R-induced endothelial permeability, elevated transepithelial electrical resistance (TEER), and increased ZO-1, Wnt3a, and β-catenin levels. Critically, Wnt3a knockdown abrogated these protective effects, establishing Wnt3a/β-catenin signaling as indispensable for Netrin-5-mediated BBB preservation. In contrast, knockdown of Netrin-5 exacerbated BBB disruption in MCAO mice and increased endothelial permeability in HBMVECs. These results position Netrin-5 as a potential therapeutic intervention for ischemic stroke.

Ionizing radiation-induced damage to the hematopoietic system is largely driven by STING activation-promoted M1 macrophage polarization and its resultant inflammation. However, effective suppression of pro-inflammatory macrophage polarization for treating radiation-induced hematopoietic stem cell injury is largely hindered by the inherent physiological barriers of bone marrow-targeted drug delivery. In this study, we develop a STING nanoinhibitor composed of poly(lactic-co-glycolic acid) nanoparticle loaded with a STING inhibitor and surface-coated senescent neutrophil membrane for targeted treatment of ionizing radiation-induced hematopoietic injury. Our STING nanoinhibitor can home to bone marrow via the CXCR4/SDF-1 axis and be phagocytosed by macrophages to shift activated pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype through suppressing cGAS-STING signaling, and this STING inhibition can further reduce radiation-induced reactive oxygen species (ROS) accumulation to reduce M2-to-M1 macrophage polarization. In irradiation-treated mouse models, the STING nanoinhibitor preferentially accumulates in bone marrow to alleviate pancytopenia, preserve bone marrow architecture, and accelerate hematopoietic recovery while avoiding significant side effects. This study highlights the targeted modulation of bone marrow macrophages as a promising strategy for promoting hematopoietic cell recovery from radiation-induced injury.

Cancer nanomedicines have improved the pharmacological performance of anticancer agents, yet their efficacy in solid tumors remains constrained by inadequate intratumoral transport and insufficiently selective payload release within dense tumor tissues. Herein, we report a nanoconfined biomineralization strategy that enables ultrasmall albumin nanocages for tumor-penetrating drug delivery and tumor-associated cathepsin B-activated therapy. With irinotecan used as a clinically relevant model payload, albumin confines the formation of irinotecan-based ionic nanocomplexes within its cavity, generating size-controllable ultrasmall nanocages. These nanocages show enhanced cellular uptake, prolonged circulation and increased tumor accumulation, and undergo accelerated irinotecan release in acidic, cathepsin B-rich lysosomal environments through proteolytic disruption of the albumin shell, thereby strengthening antitumor efficacy with reduced intestinal and hematological toxicity. Their ultrasmall architecture further promotes intratumoral distribution, modulates stromal barriers, and facilitates the subsequent delivery of macromolecular or nanoparticulate therapeutics, including anti-PD-L1 antibody and albumin-bound paclitaxel. In pancreatic and colorectal tumor models, this strategy potentiates irinotecan-based chemotherapy, clinically relevant combination regimens and immune checkpoint blockade. These findings establish nanoconfined biomineralization of albumin nanocages as an effective approach to integrate tumor penetration and tumor-associated enzyme-activated drug release for solid-tumor therapy.

Immunotherapy is an emerging strategy that awakens the intrinsic immune system for cancer treatment. Generally, successful immunotherapy of malignant tumours relies on the effective production of tumour-associated antigens and their lymph node delivery, antigen processing and presentation for T-cell activation, and the dismantling of the immunosuppressive tumour microenvironment. Toll-like receptor (TLR) agonists are potent stimulants in cancer immunotherapy, which can directly activate antigen-presenting cells (APCs) and further induce T cell activation for antitumour immune response and convert immunosuppressive tumour microenvironment to an immunogenic one for cooperative tumour ablation. However, TLR agonists for effective cancer immunotherapy have encountered essential challenges, such as insufficient immune activation and systemic side effects. In recent years, nano-immunomodulators with TLR agonists have been employed for tumour- and/or lymph node-targeted immune activation to improve the antitumour immune response and alleviate their systemic toxicities, providing a promising strategy for enhanced cancer immunotherapy. Herein, we introduce the recent progress in developing various TLR nano-immunomodulators for cancer immunotherapy via APC activation and tumour microenvironment remodelling. Upon elucidating the rational design principles of nano-immunomodulators, we elucidate the advancement of TLR nanoagonists to break the barriers in effective and safe Toll-like receptor stimulation for potent cancer immunotherapy.

Almost all high-grade gliomas, particularly glioblastoma (GBM), are highly migratory and aggressive. Migrasomes are organelles produced by highly migratory cells capable of mediating intercellular communication. Thus, GBM cells may produce migrasomes during migration. However, it remains unclear whether migrasomes can influence GBM migration and invasion. In this study, we observed the presence and formation of migrasomes in GBM cells. We found that expression levels of key migrasome formation factor, tetraspanin 4 (TSPAN4), correlated positively with pathological grade and poor prognosis of GBM based on the databases and clinical samples analysis. Subsequently, we knocked down TSPAN4 and found that GBM cell migration and invasion were significantly inhibited due to the reduced formation of migrasomes. We further confirmed that migrasomes are enriched in extracellular matrix (ECM)-related proteins such as p21-activating kinase 4 (PAK4) and laminin alpha 4 (LAMA4). Our experimental results suggest that migrasomes promote GBM cells migration by releasing such proteins into the extracellular space. Overall, we identified migrasomes in GBM and the molecular mechanisms by which they regulate them, providing potential targets for treating GBM. Observation of migrasomes in glioblastoma (GBM) and analysis of migrasome-enriched proteins revealed that migrasomes promote GBM migration and invasion by releasing the extracellular matrix-associated proteins PAK4 and LAMA4.

Cancer treatment faces significant challenges including inadequate tumor specificity, drug resistance, and severe side effects, often resulting in unsatisfactory patient outcomes. Nanomedicines offer a transformative platform for tumor-targeted drug delivery and antitumor potency activation, providing an indispensable strategy for overcoming the severe damage to normal tissues caused by the inherent "always-on" cytotoxicity of conventional therapeutic agents. This review focuses on the emerging concept of "nanoparticle-enabled in situ drug potency activation", where inactive or minimally toxic agents are selectively activated within tumors to enhance the therapeutic efficacy and minimize the adverse effects. We systematically analyzed literature from PubMed and Web of Science databases spanning the last two decades, emphasizing experimental evidence supporting this in situ drug potency activation concept. Key strategies including stimuli-responsive prodrug nanoparticles, metal-induced activation, and bioorthogonal reactions are critically evaluated for their potential to overcome limitations in current cancer therapies. The findings highlight the potential of in situ potency activation as a promising alternative to conventional therapeutics, with far-reaching implications for advancing effective and safe cancer treatments.

Cancer nanomedicine has been an emerging field for drug development against malignant tumors during the past three decades. A bibliometric analysis was performed to characterize the current international trends and present visual representations of the evolution and emerging trends in the research and development of nanocarriers for cancer treatment. This study employed bibliometric analysis and visualization techniques to analyze the literature on antitumor nanocarriers published between 2013 and 2023. A total of 98,980 articles on antitumor nanocarriers were retrieved from the Web of Science Core Collection (WoSCC) database and analyzed using the Citespace software for specific characteristics such as publication year, countries/regions, organizations, keywords, and references. Network visualization was constructed by VOSviewer and Citespace. From 2013 to 2023, the annual global publications increased 7.39 times, from 1851 to 13,683. People’s Republic of China (2588 publications) was the most productive country. Chinese Academy of Sciences (298 publications) was the most productive organization. The top 5 high-frequency keywords were “nanoparticles,” “drug delivery,” “nanomedicine,” “cancer,” and “nanocarriers.” The keywords with the strongest citation bursts recently were “cancer immunotherapy,” “microenvironment,” “antitumor immunity,” etc., which indicated the emerging frontiers of antitumor nanomedicine. The co-occurrence cluster analysis of the keywords formed 6 clusters, and most of the top 10 publications by citation counts focused on cluster #1 (nanocarriers) and cluster #2 (cancer immunotherapy). We further provided insightful discussions into the identified subtopics to help researchers gain more details of current trends and hotspots in this field. The present study processes a macro-level literature analysis of antitumor nanocarriers and provides new perspectives and research directions for future development in cancer nanomedicine.

Despite the continuous advancement of surgical resection techniques, postoperative tumor recurrence and metastasis remain a huge challenge. Here, we constructed an injectable curcumin/doxorubicin-loaded nanoparticle (NanoCD) hydrogel, which could effectively inhibit tumor regrowth and metastasis via reshaping the tumor immune microenvironment (TIME) for highly effective postsurgical cancer treatment. NanoCD was prepared by the controlled assembly of curcumin (CUR) and doxorubicin (DOX) via π-π stacking and hydrogen bonding in the presence of human serum albumin. To facilitate prolonged treatment of postsurgical tumors, NanoCD was further incorporated into the temperature-sensitive Poloxamer 407 gel (NanoCD@Gel) for intracavity administration. Mechanistically, DOX induced the generation of intracellular reactive oxygen species (ROS) and CUR reduced the ROS metabolism by inhibiting thioredoxin reductase (TrxR). The synergy of DOX and CUR amplified intracellular ROS levels and thus resulted in enhanced immunogenic cell death (ICD) of tumor cells. Upon being injected into the tumor cavity after resection, the in situ-generated NanoCD@Gel allowed the local release of CUR and DOX in a controlled manner to induce local chemotherapy and persistently activate the antitumor immune response, thereby achieving enhanced immunogenic chemotherapy with reduced systemic toxicity. Our work provides an elegant strategy for persistently stimulating effective antitumor immunity to prevent postsurgical tumor recurrence and metastasis.

The current study aimed to investigate the effects associated with SNAI2 on the proliferation of glioma stem cells (GSCs) to elucidate its underlying molecular mechanism in the development of glioma. The expression of Snail family transcriptional repressor 2 (SNAI2) in glioma tissues was initially predicted via bioinformatics analysis and subsequently confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), which revealed that SNAI2 was highly expressed in glioma tissues as well as GSCs, with an inverse correlation with overall glioma patient survival detected. Loss- and gain- of-function assays were performed to determine the roles of SNAI2 and pleckstrin homology domain and leucine rich repeat protein phosphatase 2 (PHLPP2) on GSC viability, proliferation and apoptosis. Data were obtained indicating that SNAI2 promoted the proliferation of GSCs, while overexpressed PHLPP2 brought about a contrasting trend. As detected by chromatin immunoprecipitation, RT-qPCR and agarose gel electrophoresis, SNAI2 bound to the promoter region of PHLPP2 and repressed the transcription of PHLPP2 while SNAI2 was found to inhibit PHLPP2 resulting in activation of the Akt pathway. Finally, the roles of SNAI2 and PHLPP2 were verified in glioma growth in nude mice xenografted with tumor. Taken together, the key findings of the present study suggest that SNAI2 may promote the proliferation of GSCs through activation of the Akt pathway by downregulating PHLPP2.

Background: The prognostic significance of CD44 variant-9 (CD44v9) expression in human cancers has been investigated in several studies, however, definite conclusion has not be reached. The aim of this systematic review and meta-analysis was to evaluate the prognostic significance of CD44v9 expression in various cancers. Methods: Three common databases were searched and retrieved studies were assessed using the inclusion and exclusion criteria. The further analyses for overall survival (OS), recurrence-free survival (RFS), and clinicopathological parameters were performed. Results: Fifteen studies containing 1633 cancer patients were included into this research. Patients with positive CD44v9 expression tended to have shorter OS (hazard ratio [HR] = 1.93, 95% confidence interval [CI] = 1.48-2.52,P < .01) and RFS (HR = 3.60, 95% CI = 1.52-8.53,P < .01) when compared with patients with negative CD44v9 expression. Positive CD44v9 expression was associated with larger tumor size (P = .04), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), and more advanced clinical stage (P < .01) when compared with negative CD44v9 expression. Conclusion: Positive CD44v9 expression predicted worse prognosis in human cancers compared with negative CD44v9 expression. CD44v9 expression could serve as a prognostic factor of human cancers.

Chuanhong Zhong Bei Tao Yitian Chen Zhangchao Guo Xiaobo Yang Lilei Peng Xiangguo Xia Ligang Chen 1Neurosurgery Department, Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Neurosurgical Clinical Medical Research Center of Sichuan Province, Luzhou, People’s Republic of China; 3Rheumatism Department, Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 4Department of Clinical Medicine, Medical College of Soochow University, Suzhou, People’s Republic of China Purpose: The aim of this study was to explore the potential role of B7-H3 in malignant glioma progression and identify an innovative approach in clinical glioma therapy. Methods: The protein expression of B7-H3 in highand low-grade tumor tissues from glioma patients was assessed by immunohistochemistry. The proliferative and invasive ability of B7-H3-overexpressing or knockout glioma cells was analyzed in vitro and in vivo by CCK-8 assay and an orthotopic mouse glioma model, respectively. Activation of the JAK2/STAT3/Slug signaling pathway and epithelial–mesenchymal transition (EMT) was examined by Western blotting and immunofluorescence. The anticancer effects of napabucasin (NAP) and temozolomide (TMZ) were analyzed in an orthotopic mouse glioma model. Results: The expression of B7-H3 was higher in high-grade than in low-grade tumor tissues from glioma patients. In line with this, overexpression of B7-H3 enhanced glioma cell proliferation, induced sustained glioma growth, and promoted glioma cell invasion in vitro and in vivo. Moreover, these effects were mediated through the activation of the JAK2/ STAT3/Slug signaling pathway in B7-H3 overexpression glioma cells. We also found that B7-H3 induced EMT processes through downregulation of E-cadherin and upregulation of MMP-2/-9 expression, resulting in enhanced invasion of glioma cells. Finally, we show that the combination of NAP and TMZ significantly suppressed glioma growth and glioma cell invasion, both in vitro and in vivo. Conclusion: B7-H3 overexpression facilitated sustained glioma growth and promoted glioma cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. Application of the STAT3 inhibitor NAP significantly suppressed glioma growth and invasion, and has potential as a therapeutic strategy for the treatment of glioma.

PURPOSE:The aim of this study was to explore the potential role of B7-H3 in malignant glioma progression and identify an innovative approach in clinical glioma therapy.METHODS:The protein expression of B7-H3 in high- and low-grade tumor tissues from glioma patients was assessed by immunohistochemistry. The proliferative and invasive ability of B7-H3-overexpressing or knockout glioma cells was analyzed in vitro and in vivo by CCK-8 assay and an orthotopic mouse glioma model, respectively. Activation of the JAK2/STAT3/Slug signaling pathway and epithelial-mesenchymal transition (EMT) was examined by Western blotting and immunofluorescence. The anticancer effects of napabucasin (NAP) and temozolomide (TMZ) were analyzed in an orthotopic mouse glioma model.RESULTS:The expression of B7-H3 was higher in high-grade than in low-grade tumor tissues from glioma patients. In line with this, overexpression of B7-H3 enhanced glioma cell proliferation, induced sustained glioma growth, and promoted glioma cell invasion in vitro and in vivo. Moreover, these effects were mediated through the activation of the JAK2/STAT3/Slug signaling pathway in B7-H3 overexpression glioma cells. We also found that B7-H3 induced EMT processes through downregulation of E-cadherin and upregulation of MMP-2/-9 expression, resulting in enhanced invasion of glioma cells. Finally, we show that the combination of NAP and TMZ significantly suppressed glioma growth and glioma cell invasion, both in vitro and in vivo.CONCLUSION:B7-H3 overexpression facilitated sustained glioma growth and promoted glioma cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. Application of the STAT3 inhibitor NAP significantly suppressed glioma growth and invasion, and has potential as a therapeutic strategy for the treatment of glioma.

Objective To discuss the prevalence and clinical features of pre-and post-operative mood disorders in patients with gliomas.Methods A retrospective analysis was conducted on 76 patients of gliomas who underwent surgical resection between July 2015 and June 2017 at Neurosurgery Department of the Affiliated Hospital of Southwest Medical University.Hamilton depression scale (HAMD),Hamilton anxiety scale (HAM-A) and Bech-Rafaelsen Mania rating scale (BRMS) were used for evaluation at 2-3 days before surgery and 5-7 days post surgery.Results Compared with the pre-operative conditions of 76 patients with gliomas,their postoperative HAMD scores were significantly decreased (13.5 ± 3.2 vs.9.8 ± 1.5,t =3.010,P ＜ 0.05).Significant reduction was seen in the proportion of patients with postoperative depression [42.1％ (32/76) vs.15.8％ (12/76),x2 =12.795,P ＜ 0.01].There was no significant difference between pre-and post-operative HAMA scores (10.1 ± 2.8 vs.12.8 ± 4.6) or between pre-and post-operative proportions of patients with anxiety [38.2％ (29/76) vs.50.0％ (38/76)] (both P ＞ 0.05).No significant difference was observed between pre-and post-operative BRMS score (7.5 ± 2.1 vs.8.7 ± 2.5) or pre-and post-operative proportions of patients with mania [2.6％ (2/76) vs.3.9％ (3/76)] (both P ＞0.05).The results showed that postoperative HAMD scores in pathologically high level group,frontal and temporal lobes group and right side group were significantly lower than those prior to surgery (all P ＜ 0.05).Multiple linear stepwise regression analysis showed that household income was vital to preoperative HAMD scores of glioma patients (β =-0.573,t =-3.427,P ＜ 0.01) and was negatively correlated with preoperative HAMD scores.Conclusions Some glioma patients may present with mood disorders of varying extent and types both before and after surgery.Depression seems to be closely related to the location of glioma.Family income could be an independent influencing factor for preoperative HAMD score.

Objective To explore the effect of microvascular decompression (MVD) on blood pressure in the treatment of hypertensive patients with cerebral nerve disorders and the value of preoperative MRI examination for the operation.Methods From January 2015 to October 2016,72 hypertensive patients with cerebral nerve disorders were admitted to Department of Neurosurgery,the Affiliated Hospital of Southwest Medical University and enrolled into this retrospective study.We evaluated the relationship between vessels and rostral ventrolateral medulla (RVLM) in the surgical side before operation by 3 dimensional time of flight magnetic resonance angiography (3D-TOF-MRA).Thirty cases underwent MVD of the root exit/entry zone (REZ) of the related cerebral nerves (group A) and the other 42 cases underwent exploration of RVLM or MVD of RVLM in addition to the related cerebral nerves (group B).In group B,32 cases received MVD of RVLM (group C) and the other 10 cases merely received exploration of RVLM (group D).The positive rate of preoperative MRI examination was compared between two sides.SBP (systolic blood pressure) and DBP (diastolic blood pressure) prior to operation and 12 months after operation were monitored,and the operative efficiency was evaluated.Results For preoperative MRI examination,the positive rate on the left and right sides was 87.5％ (35/40) and 65.6％ (21/32),respectively,which was was significantly higher on the left side than the right (P =0.027).The sensitivity,specificity and accuracy of 3D-TOF-MRA were respectively 85.7％ (30/35),71.4％ (5/7) and 83.3％ (35/42).The differences between preoperative and postoperative blood pressures were not statistically significant in group A (PsBP =0.067,PDBP =0.184),while they were statistically significant in group C (left side:PSBP,＜0.01,PDBP ＜0.01;right side:PsBP ＜0.01,PiDBP ＜0.01).The differences of /△BP (blood pressure change) (PΔSBP =0.425,P△DBP =0.065) and operative efficiency (P =0.703) between left side and right side were not statistically significant in group C.Conclusions MVD seems effective in treatment of neurogenic hypertension,and there is no significant difference in the therapeutic effect between left side and right side.MRI examination could he helpful for the diagnosis of neurogenic hypertension.

目的 探讨酪氨酸激酶/信号传导和转录激活子(JAK2/STAT3)信号通路在小鼠蛛网膜下腔出血(SAH)后早期脑损伤(EBI)中的作用及可能机制.方法 运用血管内穿刺法建立小鼠SAH模型.健康雄性C57BL/6J小鼠55只随机分为对照组(Control组,n=15)、手术+生理盐水组(SAH+Saline组,n=21)、手术+JAK2抑制剂组(SAH+AG490组,n=19).SAH+AG490组小鼠伤后立即给予AG490腹腔注射,SAH+Saline组腹腔注射等量生理盐水.24 h后运用疲劳转棒实验评价小鼠的神经功能;运用原位末端标记法检测神经细胞凋亡情况;运用蛋白质印迹法分析SAH后小鼠脑组织t-JAK2、p-JAK2、t-STAT3、p-STAT3的蛋白表达;运用酶联免疫吸附试验分析SAH后小鼠脑组织炎性细胞因子白细胞介素(IL)-1β、IL-6及肿瘤坏死因子α(TNF-α)的表达情况.结果 与Control组比较,SAH+Saline组小鼠出现明显的神经细胞凋亡(P＜0.05),平衡运动功能明显降低,转棒时间明显缩短(P＜0.05);进一步研究发现,JAK2和STAT3蛋白磷酸化水平升高(P＜0.05),下游炎性因子IL-1β、IL-6及TNF-α的表达水平明显升高(P＜0.05).与SAH+Saline组比较,SAH+AG490组小鼠脑组织JAK2和STAT3磷酸化水平明显降低(P＜0.05),炎性因子IL-1β、TNF-α及IL-6的表达水平明显降低(P＜0.05),小鼠神经细胞凋亡明显减少(P＜0.05),神经功能障碍明显减轻(P＜0.05).结论 小鼠SAH后早期JAK2/STAT3信号通路激活可能参与了EBI的发生、发展过程,其机制可能与调控SAH后早期的神经炎性反应有关.

BACKGROUND:LIM and SH3 protein 1 (LASP1) is upregulated in several types of human cancer and implicated in cancer progression. However, the expression and intrinsic function of LASP1 in glioblastoma (GBM) remains unclear.METHOD:Oncomine and The Cancer Genome Atlas (TCGA) database was analyzed for the expression and clinical significance of LASP1 in GBM. LASP1 mRNA and protein level were measured by qRT-PCR and western blotting. The effect of LASP1 on GBM proliferation was examined by MTT assay and colony formation assay, the effect of LASP1 on sensitivity of Temozolomide was measured by flow cytometry and subcutaneous tumor model. The association between LASP1 and PI3K/AKT signaling was assessed by western blotting.RESULTS:Oncomine GBM dataset analysis indicated LASP1 is significantly upregulated in GBM tissues compared to normal tissues. GBM dataset from The Cancer Genome Atlas (TCGA) revealed that high LASP1 expression is related to poor overall survival. LASP1 mRNA and protein in clinical specimens and tumor cell lines are frequently overexpressed. LASP1 knockdown dramatically suppressed U87 and U251 cell proliferation. Silencing LASP1 potentiated cell chemosensitivity to temozolomide in vitro, LASP1 knockdown inhibited tumor growth and enhanced the therapeutic effect of temozolomide in vivo. TCGA dataset analysis indicated LASP1 was correlated with PI3K/AKT signaling pathway, and LASP1 deletion inhibited this pathway. Combination treatment with PI3K/AKT pathway inhibitor LY294002 dramatically accelerated the suppression effect of temozolomide.CONCLUSION:LASP1 may function as an oncogene in GBM and regulate cell proliferation and chemosensitivity in a PI3K/AKT-dependent mechanism. Thus, the LASP1/PI3K/AKT axis is a promising target and therapeutic strategy for GBM treatment.