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.
Department of Gastrointestinal Medical Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Am J Med Sci. 2020 May;359(5):287-295. doi: 10.1016/j.amjms.2020.02.007. Epub 2020 Mar 13.
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.
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.
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.
Our analysis demonstrates WASF3 targeting is a new potential therapeutic strategy for gastric cancer.
胃癌是最具侵袭性的肿瘤之一，通常导致转移，而晚期胃癌的治疗仍然有限。耐药性是胃癌化疗失败的主要原因。Wiskott-Aldrich 综合征蛋白家族成员 3（WASF3）是不同癌症侵袭和转移所必需的。然而，WASF3 表达参与胃癌的研究甚少。在本研究中，我们探讨了 WASF3 在胃癌对奥沙利铂敏感性中的作用及其潜在机制。
我们使用 WASF3-siRNA 在 MGC803 细胞中沉默 WASF3。然后，通过 CCK-8、流式细胞术和 Transwell 测定研究 WASF3 沉默对 MGC803 细胞增殖、迁移、侵袭和凋亡的影响。此外，我们还评估了体外的潜在机制，以确定 WASF3 诱导的对奥沙利铂的敏感性。
小干扰 RNA 沉默 WASF3 抑制胃癌细胞的增殖、迁移和侵袭。我们还观察到 WASF3 敲低促进细胞凋亡并增强奥沙利铂敏感性。此外，WASF3 敲低诱导的奥沙利铂敏感性依赖于 Atg12 介导的自噬的抑制。
我们的分析表明，靶向 WASF3 是一种治疗胃癌的新潜在策略。
