Effect of IGF-1R inhibitor NVP-AEW541 on the dormant cells isolated from ovarian cancer xenografts
10.3781/j.issn.1000-7431.2018.11.160
- Author:
Nan ZHOU
1
Author Information
1. Department of Gynecology, Xingtai People’s Hospital
- Publication Type:Journal Article
- Keywords:
Cell proliferation;
Dormant cell;
NVP-AEW541;
Ovarian neoplasms;
Somatomedins
- From:
Tumor
2018;38(10):942-950
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effects of NVP-AEW541, an inhibitor of insulin-like growth factor 1 receptor (IGF-1R), on the proliferation and apoptosis of dormant SKOV3-PKH26hi cells isolated from ovarian cancer xenografts, and to explore the possible mechanism. Methods: The effect of NVP-AEW541 (1, 5, 10, 15 μmol/L) on the proliferation of SKOV3-PKH26hi cells was detected by CCK-8 assay. After the SKOV3-PKH26hi cells were treated with NVP-AEW541 for 48 h, FCM was performed to detect the cell cycle and apoptosis. The effects of NVP-AEW541 on the expressions of cyclin D1, caspase-3, Bax, Bcl-2, phospho-protein kinase B (p-PKB, also known as p-Akt), phospho-IGF-1R (p-IGF-1R) and phospho-glycogen synthase kinase-3β (p-GSK-3β) in SKOV3-PKH26hi cells were detected by Western blotting. Results: NVP-AEW541 had anti-proliferative effect on the SKOV3-PKH26hi cells in a dose-and time-dependent manner (both P < 0.01). NVP-AEW541 arrested the cell cycle at G0/G1 phase, and promoted the early and late apoptosis (all P < 0.01). The expressions of cyclin D1 and Bcl-2 proteins were decreased (both P < 0.05), and the expressions of caspase-3 and Bax proteins were increased (both P < 0.05) as compared with the control group (SKOV3-PKH26hi cells without any treatment). NVP-AEW541 downregulated significantly the expression levels of p-IGF-1R, p-Akt and p-GSK-3β proteins (all P < 0.01). Conclusion: IGF-1R inhibitor NVP-AEW541 is effective to inhibit the proliferation of SKOV3-PKH26hi cells and to promote apoptosis by reducing the phosphorylation level of Akt.
