下调NDRG4表达对卵巢癌细胞增殖、凋亡的影响及机制

Effects of down-regulating NDRG4 expression on proliferation and apoptosis of ovarian cancer cells

目的 观察下调N-myc下游调节基因4(NDRG4)表达对卵巢癌细胞增殖和凋亡的影响,并初步探讨其机制。方法 将卵巢癌SKOV3细胞、HO8910细胞各分为转染组和对照组,转染组细胞转染siRNA-NDRG4,对照组细胞转染无意义空白siRNA。分别于转染后0、24、48、72h,采用MTT法检测细胞增殖能力;转染48h,采用流式细胞术测算细胞凋亡率,采用Western blotting法检测凋亡相关蛋白(Bcl-2、Bax)及P38/丝裂原活化蛋白激酶(MAPK)通路相关蛋白(p-P38/MAPK、P38/MAPK)。结果 转染组SKOV3、HO8910细胞转染后48、72h增殖能力均高于相应对照组,转染48h细胞早期凋亡率、晚期凋亡率均低于相应对照组(P均<0.05)。转染组SKOV3、HO8910细胞中Bcl-2蛋白相对表达量较对照组增高,Bax蛋白、p-P38/MAPK相对表达量较对照组降低(P均<0.05)。结论 NDRG4表达下调后卵巢癌细胞增殖能力增高、凋亡减少,其机制可能与调节Bcl-2/Bax表达及P38/MAPK信号通路活性有关。

Objective To explore the effects of N-Myc downstream-regulated gene 4 (NDRG4) on the proliferation and apoptosis of human ovarian cancer cells. Methods Ovarian cell lines SKOV3 and HO8910 were each divided into the transfection group and control group. The cells in the transfection group were transfected with siRNA-NDRG4, the control group with siRNA-NC. The proliferation ability of ovarian cancer cells was detected by MTT assay at 24, 48 and 72 h after transfection. The apoptosis rate was measured by AnnexinV-FITC/PI assay. The expression of Bcl-2, Bax, P38MAPK, and p-P38MAPK was measured by Western blotting. Results The proliferation abilities of SKOV3 and HO8910 cells in the transfection group were higher than those in the control group at 48 and 72 h after transfection (both P <0.05). The early apoptosis rate and late apoptosis rate of SKOV3 and HO8910 cells in the transfection group were lower than those in the corresponding control group (both P <0.05). The relative expression of Bcl-2 protein in SKOV3 and HO8910 cells was significantly higher than that in the control group, and the relative expression of Bax protein and p-P38/MAPK was lower than that in the control group (all P <0.05).Conclusion The down-regulation of NDRG4 expression increases the proliferation and decreases apoptosis of ovarian cancer cells by regulating the Bcl-2/Bax expression and activity of P38/MAPK signaling pathway.