Abstract 4470: Targeting autophagy and apoptosis to enhance anticancer effect on esophageal carcinoma in vitro

Abstract

Abstract Esophageal cancer is one of the malignancies threatening human health with high incidence and a very low 5-year survival rate with poor outcomes in the developing countries. As one of the main treatment for esophageal cancer, chemotherapy has been played indispensable roles along with more and more chemoresistance and side effects arised though. Recent studies showed that induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Therefore targeting autophagy in cancer might be another promising approach of therapeutics. In this study, chloroquine (CQ) was used as the autophagy inhibitor, which has been the anti-malarial drug with 60 years history and safety performance, to study esophageal carcinoma cells EC109 in vivo and explore the potential molecular mechanisms. Chloroquine was employed to treat EC109 cells at different dosages and time points, and MTT results showed that the viability of EC109 was reduced dramatically in a dose dependent manner after 24 hours treatment. Moreover, we found that CQ could inhibit the migration and invasion abilities through scratch test and cell invasion Transwell chamber test, also significantly suppressed the colony formation using soft agar assay. Further investigation showed that mTOR pathway was activated with CQ exposure, and autophagy marker LC3I/II conversion decreased at early-stage, with obvious elevation eventually. More interestingly, we observed that CQ promoted the EC109 cells apoptosis by flow cytometry, also the mRNA expression of apoptosis associated proteins, such as Fas and Bax were increased. According to our findings, chloroquine showed its anticancer effect through modulating autophagy and promoting cell apoptosis, which might have promising therapeutic benefits for esophageal carcinoma. Citation Format: Yan Cai, Jiajing Cai, Qiang Ma, Yuan Xu, Dongsheng Wang, Xiaolan Guo. Targeting autophagy and apoptosis to enhance anticancer effect on esophageal carcinoma in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4470. doi:10.1158/1538-7445.AM2015-4470