Nie Hao, Wang Yu, Qin Yong, Gong Xing-Guo
Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Room 345, Hangzhou 310058, China.
Cell Biol Int. 2016 Jul;40(7):770-8. doi: 10.1002/cbin.10612. Epub 2016 May 19.
Oleanolic acid (OA), a plant-derived pentacyclic terpenoid, is known to have hepatoprotective effects. In this study, we found that OA induced autophagic cell death in multiple human gastric cancer cell lines. Moreover, OA-induced autophagy was shown for the first time in human gastric cancer cells, evidenced by the formation of GFP-RFP-LC3 puncta and autophagosomes. OA suppressed phospho-mTOR through inhibition of the PI3 K/AKT and ERK/p38 MAPK signalling pathways and through activation of the AMPK signalling pathway. Furthermore, we found that OA-induced cytotoxicity and autophagy could be blocked by the autophagy inhibitor 3-methyladenine or via siRNA targeting Beclin-1. Our in vivo research showed that OA delayed the formation of MGC-803 tumours in an autophagy-dependent manner. These results reveal a novel mechanism for OA in gastric cancer cells and suggest that OA could be a novel agent in the treatment of gastric cancer.
齐墩果酸（OA）是一种源自植物的五环三萜类化合物，已知具有肝脏保护作用。在本研究中，我们发现OA可诱导多种人胃癌细胞系发生自噬性细胞死亡。此外，OA诱导的自噬首次在人胃癌细胞中得到证实，绿色荧光蛋白-红色荧光蛋白-微管相关蛋白1轻链3（GFP-RFP-LC3）斑点和自噬体的形成即为证据。OA通过抑制磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（AKT）和细胞外信号调节激酶（ERK）/p38丝裂原活化蛋白激酶（MAPK）信号通路以及激活腺苷酸活化蛋白激酶（AMPK）信号通路来抑制磷酸化哺乳动物雷帕霉素靶蛋白（mTOR）。此外，我们发现自噬抑制剂3-甲基腺嘌呤或通过靶向Beclin-1的小干扰RNA（siRNA）可阻断OA诱导的细胞毒性和自噬。我们的体内研究表明，OA以自噬依赖的方式延迟了MGC-803肿瘤的形成。这些结果揭示了OA在胃癌细胞中的一种新机制，并表明OA可能是治疗胃癌的一种新型药物。
