Activation of caspase-4 was involved in TRAIL-induced apoptosis of gastric cancer cells
10.3969/j.issn.1001-1978.2014.10.022
- VernacularTitle:Caspase-4活化参与TRAIL诱导的胃癌细胞凋亡
- Author:
Ping WU
;
Xueping ZHU
;
Xudong ZHANG
;
Linjie ZHANG
- Publication Type:Journal Article
- Keywords:
gastric cancer;
tumor necrosis factor-relat-ed apoptosis-inducing ligand;
caspase-4;
endoplasmic reticulum stress;
apoptosis;
small interfering RNA
- From:
Chinese Pharmacological Bulletin
2014;(10):1437-1440,1441
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the potential involve-ment of caspase-4 in TRAIL ( tumor necrosis factor-re-lated apoptosis-inducing ligand )-induced apoptosis in gastric cancer cells. Methods The effect of treatment with TRAIL /z-LEVD-fmk alone or in combination for 24 h on the apoptotic rate of gastric cancer cells was detected by FCM ( flow cytometry) using propidium io-dide DNA staining. Chemically synthesized three siR-NAs targeting caspase-4 gene were transfected into gas-tric cancer cells by Lipofectamine 2000 Reagent. The efficacy of gene silencing was confirmed by Western blot analysis . The apoptotic rates of gastric cancer cells to TRAIL before and after transfection with caspase-4 siRNA were observed by FCM. The expression level of GRP78 (78-ku glucose-regulated protein) protein was examined by Western blot, the classic endoplasmic re-ticulum stress inducer tunicamycin ( TM) was used as a control. The expression levels of caspase-4 and caspase-3 after TRAIL treatment were also measured by Western blot. Results z-LEVD-fmk decreased TRAIL-induced apoptosis of gastric cancer cells signifi-cantly(P<0. 05). As compared with negative control, the expression level of caspase-4 protein was reduced after transfection, and the apoptotic rate was also de-creased ( P <0. 05 ) . While TM induced marked up-regulation of GRP78 , treatment with TRAIL resulted in, albeit to a lesser extent, increases in GRP78, in-dicative of induction of ER stress by TRAIL. Activa-tion of caspase-4 and caspase-3 occurred early after TRAIL treatment. Conclusion Activation of caspase-4 contributes to TRAIL-induced apoptosis and is asso-ciated with induction of ER stress by TRAIL in gastric cancer cells.
