Institute of Traditional Chinese Medicine & Western Medicine, School of Medicine, Yangzhou University, Jiangyang North Road, Yangzhou 225009, China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, China.
Anticancer Agents Med Chem. 2019;19(14):1754-1761. doi: 10.2174/1871520619666190731162722.
Rapamycin receptor inhibitors have been applied in the clinic and achieved satisfactory therapeutic effect recently. The mechanisms did not clearly show how the Extracts (COE) inhibited the expression of the mammalian Target of Rapamycin (mTOR) in human gastric cancer cells. The aim of this study was to investigate whether the COE inhibited the metastasis through the mTOR signaling pathway in human gastric cancer MGC-803 cells.
The abnormal expression level of mTOR protein was detected by immunohistochemistry in human gastric cancer tissue. The MGC-803/mTOR- cells were constructed by knockdown of mTOR using lentivirus infection technique. The human gastric cancer MGC-803/mTOR- cells were treated with different concentrations (20, 40, 80 μg/ml) of COE for 24 hours. The ability of cell metastasis was analyzed by the cell invasion and migration assay. The expression levels of PI3K/Akt/mTOR signaling pathway were detected by Western Blotting.
COE inhibited the proliferation, invasion and migration of MGC-803/mTOR- cells in a concentrationdependent manner. The expression of E-cadherin protein increased, and the expression of N-cadherin and Vimentin decreased simultaneously in the MGC-803/mTOR- cells. 4EBP1, p-4EBP1, P70S6k, p-P70S6k, mTOR, p-mTOR, PI3K and Akt proteins in MGC-803/mTOR- cells were reduced in a dose-dependent manner.
COE could not only inhibit cell growth, invasion and migration, but also inhibit the epithelialmesenchymal transition of gastric cancer cells. The molecular mechanism of COE inhibited the metastasis which may be related to the PI3K/Akt/mTOR signal pathway. This study provides ideas for the development of new anti-gastric cancer drugs.
雷帕霉素受体抑制剂已在临床上应用，并取得了满意的疗效。其机制尚不清楚提取物（COE）如何抑制人胃癌细胞中哺乳动物雷帕霉素靶蛋白（mTOR）的表达。本研究旨在探讨 COE 是否通过 mTOR 信号通路抑制人胃癌 MGC-803 细胞的转移。
采用免疫组织化学法检测人胃癌组织中 mTOR 蛋白的异常表达水平。采用慢病毒感染技术敲低 mTOR，构建 MGC-803/mTOR-细胞。用不同浓度（20、40、80μg/ml）COE 处理 MGC-803/mTOR-细胞 24 小时，分析细胞转移能力。Western Blotting 检测 PI3K/Akt/mTOR 信号通路的表达水平。
COE 呈浓度依赖性抑制 MGC-803/mTOR-细胞的增殖、侵袭和迁移。MGC-803/mTOR-细胞中 E-钙黏蛋白蛋白表达增加，N-钙黏蛋白和波形蛋白表达同时减少。MGC-803/mTOR-细胞中 4EBP1、p-4EBP1、P70S6k、p-P70S6k、mTOR、p-mTOR、PI3K 和 Akt 蛋白表达呈剂量依赖性降低。
COE 不仅能抑制细胞生长、侵袭和迁移，还能抑制胃癌细胞的上皮-间充质转化。COE 抑制转移的分子机制可能与 PI3K/Akt/mTOR 信号通路有关。本研究为开发新型抗胃癌药物提供了思路。
