Department of Gynaecology and Obstetrics, 232830The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China.
Department of Gynaecology and Obstetrics, 232830Henan University of Chinese Medicine, Zhengzhou City, Henan Province, China.
Hum Exp Toxicol. 2021 Dec;40(12):2156-2164. doi: 10.1177/09603271211023789. Epub 2021 Jun 16.
Endometrial cancer (EC) is the fourth most common malignancy in women in developed countries. The prognosis of EC is extremely poor, and it is an important factor that contributes to the death of patients. Therefore, studying EC pathogenesis and therapeutic targets, and exploring effective drugs are the primary tasks to improve the prognosis of EC. In the present study, we aimed to explore the function of ginkgolic acid (GA) in EC cell apoptosis and autophagy through PI3K/Akt/mTOR signal pathway in vitro and in vivo. Firstly, MTT assay and clone formation assay were employed to analyze the Ishikawa and HEC-1-B cell viabilities and proliferation after treatment with GA. The results showed that GA inhibited endometrial cancer cell survival. Flow cytometry assay and western blot assay were applied to examine the apoptosis and apoptosis related protein Bcl-2, Bax, Cleaved caspase-3 expression levels of Ishikawa and HEC-1-B cells after treatment with GA. Next, we applied western blot assay to analyze the autophagy associated proteins LC3I, LC3II, p62 and Beclin-1 in GA treated Ishikawa and HEC-1-B cells. We found that GA promoted apoptosis and induced autophagy of endometrial cancer cells. Meanwhile, western blot assay was also used to determine the expression levels of the PI3K/Akt/mTOR signal pathway related protein and the results revealed that GA inhibited the activity of PI3K/Akt/mTOR pathway. Finally, we found that GA inhibited tumor growth in vivo through immunohistochemistry assay. In conclusion, GA induces apoptosis and autophagy of EC cells via inhibiting PI3K/Akt/mTOR pathway in vivo and
子宫内膜癌（EC）是发达国家女性中第四常见的恶性肿瘤。EC 的预后极差，是导致患者死亡的重要因素。因此，研究 EC 的发病机制和治疗靶点，探索有效的药物是改善 EC 预后的首要任务。在本研究中，我们旨在通过体外和体内研究探讨银杏酸（GA）通过 PI3K/Akt/mTOR 信号通路对 EC 细胞凋亡和自噬的作用。首先，我们采用 MTT 检测和克隆形成实验分析 GA 处理后 Ishikawa 和 HEC-1-B 细胞的活力和增殖情况。结果表明，GA 抑制子宫内膜癌细胞的存活。采用流式细胞术和 Western blot 检测 GA 处理后 Ishikawa 和 HEC-1-B 细胞的凋亡及凋亡相关蛋白 Bcl-2、Bax、Cleaved caspase-3 的表达水平。接下来，我们应用 Western blot 检测 GA 处理的 Ishikawa 和 HEC-1-B 细胞中自噬相关蛋白 LC3I、LC3II、p62 和 Beclin-1 的表达水平。我们发现 GA 促进了子宫内膜癌细胞的凋亡和自噬。同时，Western blot 检测还用于确定 PI3K/Akt/mTOR 信号通路相关蛋白的表达水平，结果表明 GA 抑制了 PI3K/Akt/mTOR 通路的活性。最后，我们通过免疫组织化学检测发现 GA 通过体内抑制 PI3K/Akt/mTOR 通路抑制肿瘤生长。总之，GA 通过体内抑制 PI3K/Akt/mTOR 通路诱导 EC 细胞凋亡和自噬。
