PI3K/AKT/mTOR通路
自噬
蛋白激酶B
癌症研究
IRS1
活力测定
细胞生长
细胞凋亡
医学
化学
信号转导
生物
细胞生物学
内分泌学
胰岛素受体
胰岛素
生物化学
胰岛素抵抗
作者
Caixia Li,Chuan-Di Men,Wei Yang,Rong Chen,Jihui Zhu,Zhongping Cheng
摘要
Abstract Insulin receptor substrate 1 and 2 (IRS1/2) have been found involved in many cancers development and their inhibitors exert significant tumor‐suppressive effects. Here, we tried to explore the function of NT157, an IGF1R‐IRS1/2 inhibitor, in ovarian cancer. We treated ovarian cancer cells with varying doses of NT157. The MTT assay was employed to evaluate cell proliferation and colony formation assay was used for detecting colony‐forming ability. TUNEL assay was adopted to test cell apoptosis. Cell invasion was checked by the Transwell assay. The expression of apoptosis‐related proteins, autophagy markers, IRS1/2, and PI3K/AKT/mTOR pathway was compared by Western blot, immunofluorescence, or qRT‐PCR. As indicated by the data, NT157 abated the viability, proliferation, and induced autophagy of ovarian cancer cells. Overexpressing IRS1/2 attenuated the tumor‐suppressive effect of NT157 and heightened the PI3K/AKT/mTOR pathway activation. Inhibition of the PI3K/AKT/mTOR pathway enhanced the tumor‐suppressive effect of NT157 and facilitated NT157‐mediated autophagy. However, the autophagy inhibitor 3‐MA partly reversed NT‐157‐mediated antitumor effects. In conclusion, this study disclosed that NT157 suppressed the malignant phenotypes of ovarian cancer cells by inducing autophagy and hampering the expression of IRS1/2 and PI3K/AKT/mTOR pathway.
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