Previous studies have shown that some dysregulated miRNAs are involved in radioresistance of tumor cells. Here, we identified significantly decreased miR-424 expression in radioresistant cervical cancer cells and specimens from cervical cancer patients with radioresistance compared to their radiosensitive parental cells and specimens from radiosensitive patients, respectively. Ectopic expression of miR-424 significantly increased radiation-induced DNA damage, cell apoptosis and G2/M cell cycle arrest in radioresistant cervical cancer cells. Notably, miR-424 agomiR treatment can sensitize radioresistant cervical cancer cells to radiation in a xenograft model. Furthermore, we demonstrated that miR-424 regulated radiosensitivity by directly targeting aprataxin. Taken together, these findings suggest that miR-424 acts as a radiosensitizing miRNA and reveal a new therapeutic strategy for radioresistant cervical cancers.

Radiotherapy in osteosarcoma patients is problematic due to radioresistance; therefore, understanding the mechanism of radioresistance is integral to providing effective radiotherapeutic regimens for osteosarcoma. We now report the activity of an miRNA, miR-513a-5p, in stimulating radiosensitivity of osteosarcoma cells in vitro and in vivo. MiR-513a-5p expression is decreased in osteosarcoma tissue from patients and cultured osteosarcoma cell lines. However, exogenous re-expression of this miRNA in osteosarcoma cell lines, including HOS, U2OS and 9901, can induce sensitization to ionizing radiation. We also confirm that miR-513a-5p suppresses APE1 expression, and that both the redox and DNA repair activity of APE1 were decreased in miR-513a-5p expressing cell lines. By suppressing APE1, miR-513a-5p induces the DNA damage response which stimulates apoptosis after irradiation. Our report establishes miR-513a-5p as a radiosensitizing miRNA and identifies its activity in the suppression of APE1, which could directly lead to radiosensitization.

Purpose To define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy. Results Our investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010). Experimental Design We measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control. Conclusions Our studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naïve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.

Genistein (GEN) has been previously shown to have a proapoptotic effect on cancer cells through a p53-dependent pathway, the mechanism of which remains unclear. One of its intracellular targets, APE1, protects against apoptosis under genotoxic stress and interacts with p53. In this current study, we explored the mechanism of the proapoptotic effect of GEN by examining the APE1–p53 protein–protein interaction. We initially showed that the p53 protein level was elevated in GEN-treated human non-small lung cancer A549 cells and cervical cancer HeLa cells. By examining both protein synthesis and degradation, we found that GEN enhances p53 intracellular stability by interfering with the interaction of APE1 and p53, which provided a plausible explanation for how GEN initiates apoptosis. Furthermore, we found that the interaction between APE1 and p53 is important for the degradation of p53 and is dependent on the redox domain of APE1 by utilizing the redox domain mutant APE1 C65A. Our data suggest that the degradation of wild-type p53 is blocked when the redox domain of APE1 is masked or interrupted. Based on this evidence, we hereby report a novel mechanism of p53 degradation through an APE1-mediated, redox-dependent pathway.

Single-nucleotide polymorphisms (SNP) of the gene belonging to the BCL2 family are thought to play a role in chemotherapy resistance. This study investigated the association of BCL2-938C>A(rs2279115) and BAX-248G>A(rs4645878) promoter region SNPs and the clinical responses and outcomes of 235 non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. The data suggested that BAX-248GA and GA+AA genotype was associated with poor response [odds ratio (OR) 1.943, p = 0.039; OR 1.867, p = 0.038, respectively] to chemotherapy and BCL2-938CA, CA+AA and BAX-248GA, AA and GA+AA were associated with poor progression-free survival (PFS) [hazard ratio (HR) 1.514, p = 0.004; HR 1.456, p = 0.009; HR 1.449, p = 0.013; HR 2.006, p = 0.010; HR 1.506, p = 0.003, respectively] and BCL2-938CA, AA and CA+AA and BAX-248GA, AA and GA+AA were associated with poor overall survival (OS) (HR 2.006, p < 0.001; HR 2.322, p < 0.001; HR 2.096, p < 0.001; HR 1.632, p = 0.001; HR 2.014, p = 0.010; HR 1.506, p < 0.001, respectively). Furthermore, combination of these two polymorphisms showed patients with 2–4 variant alleles of these two genes associated with poor PFS and OS (HR 1.637, p = 0.001; HR 2.365, p < 0.001). The data from the current study provide evidence that BCL2-938C>A and BAX-248G>A polymorphisms may be useful in predicting clinical outcomes of patients with advanced inoperable NSCLC to platinum-based chemotherapy.

AT-101 is a BH3 mimetic and pan-Bcl-2 inhibitor that has shown potent anticancer activity in non-small-cell lung cancer (NSCLC) in murine models, but failed to show clinical efficacy when used in combination with docetaxel in NSCLC patients. Our recent study has demonstrated that AT-101 enhanced the antitumor effect of cisplatin (CDDP) in a murine model of NSCLC via inhibition of the interleukin-6/signal transducer and activator of transcription 3 (STAT3) pathway. This study explored the underlying mechanisms for the enhanced anticancer activity of CDDP by AT-101. Our results show that, when compared with monotherapy, AT-101 significantly enhanced the inhibitory effects of CDDP on proliferation and migration of A549 cells and on tube formation and migration in human umbilical vein endothelial cells. AT-101 promoted the proapoptotic activity of CDDP in A549 cells. AT-101 also enhanced the inhibitory effect of CDDP on DNA repair and redox activities of apurinic/apyrimidinic endonuclease 1 (APE1) in A549 cells. In tumor tissues from nude mice treated with AT-101 plus CDDP or monotherapy, the combination therapy resulted in greater inhibition of angiogenesis and tumor cell proliferation than the monotherapy. These results suggest that AT-101 can enhance the antitumor activity of CDDP in NSCLC via inhibition of APE1 DNA repair and redox activities and by angiogenesis and induction of apoptosis, but other mechanisms cannot be excluded. We are now conducting a Phase II trial to examine the clinical efficacy and safety profile of combined use of AT-101 plus CDDP in advanced NSCLC patients.

Objective To explore the risk factors of skeletal related events (SREs) in non small cell lung cancer with bone metastases and its effect on the prognosis .Methods Totally 223 cases of NSCLC patients with bone metastasis were retrospective studied from January 2010 to December 2012 in our hospital .The clinical features ,predictive factors for SREs were analysed by sin‐gle factor and multifactor analysis .Results Among 223 cases of NSCLC patients with bone metastasis ,119 cases occured with SREs(53 .4% ) .Univariate analysis showed that the occurrence of SREs in female ,no smoker ,adenocarcinoma ,solitary bone metas‐tasis lesions were less than the male ,smoker non‐adenocarcinoma ,and multiple bone metastases (P<0 .05) ,but the rost without statistically significant(P>0 .05) .The multivariate analysis revealed only multiple bone metastases was an independent risk factor for SREs .The median survival time of the NSCLC patients with bone metastasis was 15 .3 months .Moreover ,survival analysis showed that SREs had no statistical significance on the prognosis of bone metastasis in NSCLC patients (P>0 .05) .Conclusion The female ,adenocarcinoma ,smoking history ,solitary bone metastasis lesions occurred in patients with lower risk SREs .Multiple bone metastasis is an independent risk factor for SREs ,attention should be paid to monitoring and prevention .

Objective To investigate the expression of alpha‐fetoprotein(AFP) in various people and situations along with other item of multiple tumor marker protein chip ,and to explore its clinical significance .Methods Totally 25 076 cases detected with multiple tumor markers chip from December 2003 and July 2011 were collected .The expression of AFP and its combination with other item of multiple tumor marker protein chip were analyzed in malignant tumors and other people .Results Elevated AFP in patients with malignant tumors(17 .3% ) was significantly higher than in benign lesions(15 .3% ) and normal persons(12 .1% ) ,a‐mong them ,the AFP rise rate was highest for liver cancer (54 .3% ) ,and the difference was statistically significant (P<0 .01) ,fol‐lowed by ovarian cancer(18 .8% ) and gastric cancer(17 .1% ) .The positive of AFP was commonly combined with other item elevat‐ed in patients with malignant tumors .The most common accompanied item was CA125 ,followed by CA199 ,CEA ,Ferritin ,CA242 , CA15‐3 ,there was no statistically significant between CA242 and CA15‐3(P> 0 .05) .AFP/CA125 was most common pancreatic cancer (60 .5% ) and ovarian cancer (46 .2% ) ,AFP/CA19‐9 was most common in pancreatic cancer (58 .1% ) and liver cancer (43 .7% ) .AFP + CA19‐9 + CA125 was most common in liver cancer (17 .9% ) .Conclusion AFP increase alone was significantly valuable to diagnosis liver cancer ,moreover it combined with CA19‐9 or CA125 may help to improve the positive rate in pancreatic and ovarian cancer .

Objective To analyze the clinical features ,characteristics of diagnosis and treatment ,and prognos‐tic factors of stage Ⅳa non‐small cell lung cancer (NSCLC) .Methods 301 patients with initially diagnosed stage Ⅳa NSCLC in our hospital from October 2009 to December 2013 were analyzed on the clinical characteristics ,diagnosis and treatment situation ,including the main observation indicators of occurrence rate ,effective rate ,progression free survival(PFS) and overall survival(OS) .Results The median PFS of stage Ⅳa NSCLC was 3 .3 months (95% CI:2 .808-3 .792) and the median OS was 7 .8 months (95% CI:6 .700-8 .900) .The multivariable Cox regression anal‐ysis showed that the performance status(PS) score ,whether pleural effusion(PE) controllable ,whether accepting 4 weeks or more chemotherapy were the independent factors affecting the disease progress and OS ,the tyrosine kinase inhibitor(TKI) therapy also was an independent prognostic factor of OS .Conclusion The median OS of stage Ⅳa is 7 .8 months .For patients carrying EGFR gene mutation ,using the TKI treatment is beneficial .For patients with good PS ,controlling PE and systemic chemotherapy are beneficial for improving OS .

Angiogenesis plays an important role in tumor growth and metastasis and has been reported to be inversely correlated with overall survival of osteosarcoma patients. It has been shown that apurinic/apyrimidinic endonuclease 1 (APE1), a dually functional protein possessing both base excision repair and redox activities, is involved in tumor angiogenesis, although these mechanisms are not fully understood. Our previous study showed that the expression of transforming growth factor β (TGFβ) was significantly reduced in APE1-deficient osteosarcoma cells. Transforming growth factor β promotes cancer metastasis through various mechanisms including immunosuppression, angiogenesis, and invasion. In the current study, we initially revealed that APE1, TGFβ, and microvessel density (MVD) have pairwise correlation in osteosarcoma tissue samples, whereas TGFβ, tumor size, and MVD were inversely related to the prognosis of the cohort. We found that knocking down APE1 in osteosarcoma cells resulted in TGFβ downregulation. In addition, APE1-siRNA led to suppression of angiogenesis in vitro based on HUVECs in Transwell and Matrigel tube formation assays. Reduced secretory protein level of TGFβ of culture medium also resulted in decreased phosphorylation of Smad3 of HUVECs. In a mouse xenograft model, siRNA-mediated silencing of APE1 downregulated TGFβ expression, tumor size, and MVD. Collectively, the current evidence indicates that APE1 regulates angiogenesis in osteosarcoma by controlling the TGFβ pathway, suggesting a novel target for anti-angiogenesis therapy in human osteosarcoma.

e14608 Background: Rectal cancer represents 30% of all colorectal cancers, with about 40,000 new cases per year. In the past two decades the management of rectal cancer has made important progress highlighting the important role of a multimodal strategic approach that combines surgery, radiation therapy and chemotherapy. Nowadays, surgery remains the primary treatment and neo-adjuvant chemoradiotherapy, based on fluoropyrimidine continuous infusion, is considered the standard in locally advanced rectal cancer (LARC). Arterial infusion through the superior rectal artery is conventionally used in palliative care of inoperable LARC, while its application in neoadjuvant therapy of LARC remains unreported. Methods: Twenty-four patients with LARC (clinically T3-4, any N) were randomized in two arms: those treated with neoadjuvant concurrent systematic chemoradiotherapy consisting of 46Gy/23/ff concurrent with S1 (40-60 mg bid) and on days 1-28 (NACT-RT) or concurrent superior rectal artery chemotherapy infusion (oxaliplatin 85 mg/sqm) with oral S1 and radiotherapy with the same regime (NATACE-RT). Surgery was performed after 4-6weeks. The primary end point for the current report was the pathological response. Results: Twenty out of 24 patients were evaluated (NACT-RT 10, NATACE-RT 10); 10/14 in the NACT-RT arm and all patients in the NATACE-RT arm received the preoperative treatment as in the protocol and underwent a radical resection. One out of 10 in the NACT-RT group showed a complete pathologic response (pCR), whereas 9/10 in the NATACE-RT group showed a pCR. The overall downstaging rates did not show any significant difference between the two arms. The OS and DFS are under observation. Conclusions: The current pilot study suggests that the application of TACE in patients with LARC significantly increases the pCR when compared with conventional NACT-RT and is associated with better tolerance and an equal downstaging effect.

e15253 Background: The aim of this study was to investigate the efficacy and safety of capecitabine combined with recombinant human endostatin (endostar) and stereotactic radiotherapy to treat locally advanced pancreatic cancer. Methods: Patients aged 40 years or older with histologically diagnosed locally advanced pancreatic cancer recruited in Daping Hospital from October 2013 to October 2014 were eligible for enrollment in this single-arm phase 2 trial. Patients received capecitabine (1000 mg/m2 twice daily) concurrented with endostar (3ml concentrate to 500ml saline, uniform intravenous drip, drip time 3-4 hours) for 14 days and repeat every 21 days for 6 cycles. Stereotactic radiotherapy was applied to the local lesion of the pancreas with a total dose of 40 Gy in 10 fractions. The primary end point was progression-free survival (PFS), secondary end points included overall survival (OS), time to treatment failure (TTF) and safety, analysed by intention to treat including only those patients with valid CT assessments. This trial is registered with ChiCTR, number ChiCTR-ONC-13003720. Results: Thirteen patients were evaluable for responses. Median PFS was 10.0 months (95% CI 5.01-14.99), median OS was 20.0 months (95% CI 2.52-37.48) and median TTF was 10 months (95% CI 3.35-16.65). Grade 3/4 hematological and non-hematological toxicities were rare. All the side effects were tolerable and reversible. Conclusions: The combination of radio-chemotherapy and endostar has potential survival benefit in patients with locally advanced pancreatic cancer receiving capecitabine. Clinical trial information: ChiCTR-ONC-13003720.

This retrospective study was conducted to determine whether endostatin improves the efficacy and safety of platinum-based chemotherapy administered via both intravenous and arterial infusions for stage III/IV non-small-cell lung cancer (NSCLC). Seventy one patients with confirmed pathological or cytological diagnosis of NSCLC from January 2008 to March 2013 were enrolled for the study. Patients received three different therapeutic regimens until disease progression or an intolerable toxicity was evidenced. Group C received chemotherapy administered by intravenous injection and subsequent radiotherapy. Group IC received chemotherapy by intravenous injection and arterial infusion plus radiotherapy. Group IC + E patients were treated with chemotherapy plus Endostatin injected arterially and intravenously and subsequent radiotherapy. Group IC + E showed a progression-free survival (PFS) of 12 months as compared to 7 months of group C, a significant increase indeed ( p = 0.037). Likewise, the overall survival time higher in Group IC + E and Group IC was compared to Group C ( p = 0.001; p = 0.004, respectively). The adverse or toxic side effects exhibited by Group IC + E were not significantly different from either Group IC or Group C. Endostatin administered in combination with chemotherapeutic agents via both intravenous injection and arterial infusion enhanced the PFS and OS in advanced NSCLC without increasing the risk of toxicity.

Introduction Gastric cancer is a fatal malignancy with a rising incidence rate. Effective methods for early diagnosis, monitoring metastasis, and prognosis are currently unavailable for gastric cancer. In this study, we examined the association of programmed death ligand-1 (PD-L1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with the prognosis of gastric cancer. Methods The expressions of PD-L1 and APE1 were detected by immunohistochemistry in 107 cases of human gastric carcinoma. The correlation of PD-L1 and APE1 expression with the clinicopathologic features of gastric carcinoma was analyzed by SPSS version 19.0. Results The positive expression rates of PD-L1 and APE1 in gastric cancer tissues were 50.5% (54/107) and 86.9% (93/107), respectively. PD-L1 and APE1 positive expressions were significantly associated with depth of invasion, lymph node metastasis, pathological type, overall survival, and higher T stage. Furthermore, the expression of PD-L1 in highly differentiated gastric cancers was higher than that in poorly differentiated cancers (P=0.008). Moreover, the expression of APE1 and PD-L1 in gastric cancers was positively correlated (r=0.336, P<0.01). Multivariate analysis showed that the depth of invasion was a significant prognostic factor (risk ratio 19.91; P=0.000), but there was no significant relationship with PD-L1, APE1, prognosis, and other characteristics. Conclusion The deregulation of PD-L1 and APE1 might contribute to the development and the poor prognosis of gastric cancer. Our findings suggest that high expression of PD-L1 and APE1 is a risk factor of gastric cancer and a new biomarker to predict the prognosis of gastric cancer. Furthermore, our findings suggest that targeting the PD-L1 and APE1 signaling pathways may be a new strategy for cancer immune therapy and targeted therapy for gastric cancer, especially in patients with deep invasion and lymph node metastasis.

[目的]总结女性晚期非小细胞肺癌患者的临床特征及治疗效果,分析影响预后的因素,为女性晚期非小细胞肺癌的个体化分层治疗提供依据.[方法]回顾性分析女性晚期非小细胞肺癌178例,收集资料包括年龄、病理类型、EGFR突变情况、肿瘤分期、一线治疗效果、无进展生存期(PFS)和总生存期(0S).[结果]患者平均年龄58.0±11.3岁;腺癌占87.1％;接受EGFR基因检测患者中突变型占60.8％(31/51);Ⅳ期患者占75.9％.接受针对肿瘤的治疗的169例患者中,一线治疗后客观有效率为52.3％,疾病控制率为84.9％.中位PFS为9.0个月,中位OS为22.0个月.Cox回归多因素分析显示:年龄、治疗线数和一线治疗效果均为OS独立预后因素(P＜0.05).一线治疗进展后继续接受抗肿瘤治疗的患者的OS较终止治疗的患者显著延长(P＜0.05).[结论]女性晚期非小细胞肺癌以腺癌为主,EGFR突变率较高,一线治疗效果、接受治疗线数对于女性晚期非小细胞肺癌有独立预后意义,一线治疗进展后继续接受抗肿瘤治疗的患者预后更好.

Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (≥ 24 kg/m2). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m2). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.

Objective To construct the lentivirus vector containing the hsa‐miR‐424 gene ,and identify the expression level of miR‐424 in cells .Research the influence of hsa‐miR‐424 on proliferation of cervical cancer Hela cell line .Methods Using the human genomic DNA as template to design the upper and lower primers for synthesis of miR‐424 ,and amplifying the target fragment by polymerase chain reaction (PCR) .Recover the products and conduct sequencing after connecting it into the pMD18T vector .Ampli‐fy the product by PCR template as pMD18T‐miR424 ,and insert the fragment expressing pMD18T‐miR424 into the vector of pLen‐tis‐CMV‐GFP‐MCS‐PGK‐PURO after enzyme cutting to construct the pLentis‐CMV‐GFP‐miR424‐PGK‐PURO .Package the com‐pound with pMD2 .G and pSPAX2 in 293T cell to produce the lentivirus ,and using the supernatant containing lentivirus to infect the Hela cell line .Results The sequencing result proved the sequence of miR‐424 in plasmid vector was correct ,which proved the construction of lentivirus was successful and the target lentivirus was obtained .The expression of miR‐424 almost rise 60 times af‐ter infected the cervical cancer Hela cell by the carrier .The result of M TT method suggested :the cervical cancer Hela cell lines have slowed proliferation with infection miR‐424 lentivirus .Conclusion The miR‐424 lentivirus vector was constructed successfully and the high efficacy expression miR‐424 cell line was established and stable .The cervical cancer Hela cell were infected with the super‐natant containing lentivirus ,inhibited the proliferation of Hela cell successfully ,and laid a good foundation for subsequent research .

Accumulative evidence suggests that polymorphism in the APE1 gene may have association with the etiology of lung cancer by modulating DNA repair capacity. Many studies have evaluated the association with great discrepancies in the results. The present meta-analysis was undertaken to clarify the effects of this polymorphism on lung cancer. A meta-analysis of 15 studies with 4,932 lung cancer patients and 6,555 cancer-free controls was conducted to evaluate the strength of the association using odds ratios (ORs) with 95 % confidence intervals (CIs). Overall, no significant association was found between APE1 polymorphism and lung cancer risk. We also did not observe any statistical evidence of modified lung cancer risk either in smokes or in nonsmokers. In the stratified analysis by ethnicity, however, it was found that the Glu/Clu genotype carriers had 1.16-fold higher risk of suffering lung cancer compared with the carriers of Arg/Glu + Arg/Arg genotypes in Asian population (OR = 1.16, 95 % CI = 1.01-1.32, P = 0.242). This meta-analysis provides statistical evidence for a potential association between APE1 polymorphism and an increased risk of lung cancer in Asian population.

AT-101, known as R-(-)-gossypol, is a potent anticancer agent, but its chemosensitizing effects remain elusive. The present study aimed to examine whether AT-101 could increase the sensitivity of non-small cell lung cancer A549 cells to cisplatin (CDDP) and the underlying mechanisms. We evaluated the efficacy of the sequential treatment with AT-101 and CDDP using both in vitro and in vivo models. Our results showed that as compared to AT-101 or CDDP monotherapy, or AT-101 plus CDDP concurrent treatment, the sequential treatment significantly inhibited cell proliferation and migration and induced tumor cell death. Moreover, the efficacy of the sequential treatment was also confirmed in a mouse A549 xenograft model. Our study revealed that AT-101 inhibited the reduced status of apurinic/apyrimidinic endonuclease 1 (APE1) and attenuated APE1-mediated IL-6/STAT3 signaling activation by decreasing IL-6 protein expression; suppressing the STAT3-DNA binding; and reducing the expression of the downstream antiapoptotic proteins Bcl-2 and Bcl-xL. In conclusion, AT-101 enhances the sensitivity of A549 cells to CDDP in vitro and in vivo through the inhibition of APE1-mediated IL-6/STAT3 signaling activation, providing a rationale for the combined use of AT-101 and CDDP in non-small cell lung cancer chemotherapy.

Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum–paclitaxel treatment.