Effects of gastrokine-2 expression on gastric cancer cell apoptosis by activation of extrinsic apoptotic pathways

Abstract

Gastrokine-2 is a putative gastric cancer-specific tumor suppressor gene, the loss of which is known to be involved in the development and progression of gastric cancer, and restoration of gastrokine-2 expression inhibits growth of gastric cancer cells in vitro. However, the underlying mechanism of these effects requires elucidation. In the present study, expression patterns of gastrokine-2 protein were examined in gastric cancer tissues and cell lines. Expression of gastrokine-2 was restored in gastric cancer cells in order to assess its effect on cell viability, apoptosis and gene expression. A total of 76 gastric cancer tissues with corresponding normal mucosae samples, and two gastric cancer cell lines (SGC-7901 and AGS) were subjected to western blot analysis of gastrokine-2 expression. SGC-7901 cells were transiently transfected with gastrokine-2 cDNA and then treated with anti-CD95 and/or anti-Fas antibodies prior to analysis of cell viability, apoptosis and gene expression levels. Expression of gastrokine-2 protein was reduced or absent in gastric cancer tissues and gastric cancer cell lines. Following restoration of gastrokine-2 expression, the protein expression level of Fas was significantly increased, but no marked change was observed in the levels of bcl-2 and Bax proteins. Expression of gastrokine-2 protein reduced gastric cancer cell viability and induced apoptosis. Activity of caspase-3 and caspase-8 was increased, but caspase-9 activity remained unchanged in the SGC-7901 cells. Reduction or knockout of gastrokine-2 protein expression may contribute to gastric cancer development or progression, as the current study demonstrated that restoration of gastrokine-2 expression induces apoptosis of gastric cancer cells through the extrinsic apoptosis pathway.

Fas expression is downregulated in gastric cancer

“…Furthermore, a previous study reported that Fas facilitates the caspase-8 dimerization and maturation process (30). The present study demonstrated that Fas expression was correlated with caspase-8 expression and this was consistent with previously reported data (28–30). …”

“…The present study demonstrated that the caspase-8 expression was lower in gastric cancer tissues compared with healthy gastric tissues and was correlated with Fas expression in gastric cancer tissues and cell lines. Previous studies revealed that functional grade purified Fas activated caspase 8 in extrinsic apoptosis, and recruited procaspase-8 to form DISC in extrinsic apoptosis in gastric cancer cells (28,29). Furthermore, a previous study reported that Fas facilitates the caspase-8 dimerization and maturation process (30).…”

Heterodimeric interaction between GKN2 and TFF1 entails synergistic antiproliferative and pro-apoptotic effects on gastric cancer cells

“…Shi et al have demonstrated that GKN2 may induce apoptosis by activating Fas, caspase-3, and caspase-8 [33]. In this study, ectopic TFF1 expression was linked to a considerably elevated percentage of apoptotic cells compared to a mock control (Fig.…”

Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis in Ec9706 and Eca109 esophageal carcinoma cells

“…The efficacy of chemotherapy drugs can be evaluated by their ability to induce apoptosis. The upregulation of caspase-3 and the reduction of mitochondrial membrane potential may result in apoptosis, so an ideal chemotherapy drug would cause these alterations (16,17).…”