Inhibitory effect of apatinib on HCT-116 cells and its mechanism.
- Author:
Liang YIN
1
;
Jin WANG
;
Feng-Chang HUANG
;
Yun-Fei ZHANG
;
Ning XU
;
Zheng-Qi WEN
;
Wen-Liang LI
;
Jian DONG
Author Information
- Publication Type:Journal Article
- From: Journal of Southern Medical University 2017;37(3):367-372
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.
METHODSThe cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.
RESULTSApatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an ICvalue of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.
CONCLUSIONApatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.