Yanli Nie1, Xinjun Liang2, Sanhe Liu2, Fang Guo3, Na Fang3, Fuxiang Zhou4. 1. Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China; Department of Gastrointestinal Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Gastrointestinal Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3. Department of Pathology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China. Electronic address: fxzhouwhu@gmail.com.
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. CONCLUSIONS: Our analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.
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. CONCLUSIONS: Our analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.