WASF3 knockdown sensitizes gastric cancer cells to oxaliplatin by inhibiting ATG12-mediated autophagy

Abstract Background Gastric cancer is one of the most aggressive tumors, usually resulting in metastasis, and therapies for advanced gastric cancer remain limited. Drug resistance is the main reason for chemotherapeutic failure in gastric cancer. Wiskott-Aldrich syndrome protein family member 3 (WASF3) is required for invasion and metastasis of different cancers. However, there has been little study of WASF3 expression involvement in gastric cancer. In this study, we explored the role of WASF3 in the sensitivity of gastric cancer to oxaliplatin, and the underlying mechanisms. Methods We silenced WASF3 using WASF3-siRNA in MGC803 cells. Then, CCK-8, flow cytometry and transwell assay were performed to study the effect of WASF3 silencing on proliferation, migration, invasiveness, and apoptosis of MGC803 cells. Moreover, we evaluated the potential mechanism in vitro to determine the sensitization to oxaliplatin induced by WASF3. Results WASF3 silencing by small interfering RNA inhibited the proliferation, migration, and invasiveness of gastric cancer cells. We also observed that WASF3 knockdown promoted cell apoptosis and enhanced oxaliplatin sensitivity. Furthermore, the sensitization to oxaliplatin induced by WASF3 knockdown depended on the inhibition of Atg12-mediated autophagy. Conclusion Our analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.