Impact of RNAi-Targeted Silencing of Survivin and Hypoxia-Inducible Factor-1α on the Biological Behaviors of Gastric Cancer SGC-7901 Cells In Vitro

Abstract Hypoxia-inducible factor-1 (HIF-1) plays crucial roles in the primary transcriptional responses to hypoxia stress by modulating hypoxia gene expression. Survivin is regarded as an effector downstream of HIF-1 that promotes cell survival under hypoxia conditions. HIF-1α and survivin are proposed as potential targets in the treatment of gastric cancer. This study was designed to investigate the anticancer effects of RNA interference targeting survivin and HIF-1α on the gastric cancer cell line, SGC-7901 under hypoxia. In this study, cultured cells were divided randomly into four groups: a blank control group, a scrambled siRNA (SCR) control group, a siRNA-Survivin group (ss group) and a siRNA-Survivin+siRNA-HIF-1α group (sis+siH group). The siRNA targeting survivin and/or HIF-1α genes were transfected into SGC-7901 cells. The expression of survivin and HIF-1α was identified by RT-PCR and Western blotting assay. Apoptosis was determined by flow cytometry. The invasion and migration abilities of the cells were evaluated by transwell and wound healing assays, respectively. Cell growth curves were determined by MTT assay at 48 h indicated that the viability of the SGC-7901 cells was inhibited in a time-dependent manner with a highest inhibitory rate of 82.1 ± 0.85 % at 48 h. The siRNA targeting the survivin gene decreased the expression of survivin and the combined transfection of siRNA targeting survivin and HIF-1α down-regulated the expression of both survivin and HIF-1α (P < 0.05). Compared with the blank control group, the combined siRNA groups exhibited obvious features with decreased invasion and migration abilities (P < 0.05). The apoptosis rate increased and the cell proliferation decreased following gene silencing (P < 0.05). The down-regulation of survivin and HIF-1α may induce an anticancer effect in SGC-7901 cell lines by enhancing cell apoptosis and decreasing proliferation, migration and invasion ability.