The role of Notch signaling pathway in insulin regulation of endometrial cancer cell growth and apoptosis
10.3969/j.issn.1671-8348.2017.29.005
- VernacularTitle:Notch信号通路在胰岛素调节子宫内膜癌细胞生长及凋亡中的作用
- Author:
Lin YANG
1
;
Yin SHAO
;
Lifei WANG
Author Information
1. 广东省深圳市人民医院妇科 518000
- Keywords:
endometrial neoplasms;
insulin;
γ-secretase inhibitor MW167;
Notch signaling;
cell proliferation
- From:
Chongqing Medicine
2017;46(29):4047-4050
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of Notch signaling pathway on proliferation of insulin-induced endometrial carcinoma cells and apoptosis related protein expression levels.Methods The endometrial carcinoma Ishikawa 3-H-12 cell line was primarily cultured and subcultured in vitro.Then,the cultured cells were divided into five groups:the control group (3 mL PBS was added into the group),the insulin group (cells were stimulated by 1 × 106 mol/L insulin) and MW167 groups (different doses of γ-secretase inhibitor MW167 pretreated with insulin stimulation).After 48 h culturation,inhibition of endometrial carcinoma cell growth of each group was measured by MTT-colorimetric method,the apoptosis-related proteins (Caspase-3,Caspase-8) and Notch1 protein expression levels of each group were determined by Western blot.Results Insulin can promote Notch1 protein expression in endometrial carcinoma cells,after 48 h insulin stimulation,the Notch1 protein expression level was significantly higher than that in the control group (P＜0.05).MW167 can inhibit insulin-induced Notch1 protein expression in a concentration-dependent inhibition manner.The absorbance at 570 nm (A570) of endometrial carcinoma cells cultured for 24,48 and 72 h in different groups were significantly different (P＜0.05).The A570 values in the insulin group at each time point were higher than those in the control group (P＜0.05),and the insulin-induced endometrial carcinoma cell proliferation reached its highest level at 48 h.MW167 inhibited insulin-induced endometrial carcinoma cells proliferation in a concentration-and time-dependent manner,and 20 μmol/L MW167 persistently inhibited insulin-induced proliferation of endometrial carcinoma cells at 48 h.Western blot analysis showed that expression levels of Caspase-3 and Caspase-8 protein in the insulin group at each time point were lower than those in the control group (P＜0.05),and MW167 promoted the expressions of Caspase-3 and Caspase-8 in a concentration-and time-dependent manner.Conclusion MW167 can suppress the insulin-induced endometrial carcinoma cells proliferation and promote the expression of related apoptotic proteins by inhibiting Notch signaling pathway,and induce apoptosis of endometrial carcinoma ceils.
