胰岛素样生长因子1受体(IGF-1R)基因表达对脉络膜黑色素瘤细胞增殖、凋亡及STAT3信号通路的调控作用  

IGF-1R gene expression inhibits the proliferation and promotes apoptosis of choroidal melanoma through inhibition of STAT3 signaling pathway

作　　者：任耘 蔡明高[2] 霍鸣[3] REN Run;CAI Ming-Gao;HUO Ming(Department of Ophthalmology,Dangyang People’s Hospital,Dangyang 444100,Hubei Province,China;Department of Ophthalmology,People’s Hospital of Wuhan University,Wuhan 430030,Hubei Province,China;Medical College of China Three Gorges University,Yichang 443002,Hubei Province,China)

机构地区：[1]当阳市人民医院眼科,湖北省当阳市444100 [2]武汉大学人民医院眼科,湖北省武汉市430030 [3]三峡大学医学院,湖北省宜昌市443002

出　　处：《眼科新进展》2018年第11期1024-1027,共4页Recent Advances in Ophthalmology

摘　　要：目的探讨胰岛素样生长因子1受体(insulin-like growth factor 1 receptor,IGF-1R)基因表达对脉络膜黑色素瘤(choroidal melanoma,CM)细胞增殖、凋亡及STAT3信号通路的调控作用。方法参照Lipofectamine^(TM)2000说明将干扰IGF-1R表达的siRNA转染人CM细胞OCM-1作为IGF-1R-siRNA组,并设置无干扰作用的siRNA及加入脂质体的细胞作为阴性对照组和空白对照组,AG490作为STAT3信号通路抑制剂,收集转染48 h的细胞,通过CCK8法及流式细胞仪分别检测细胞活力及细胞凋亡率;Western blot检测STAT3信号通路磷酸化的p-JAK2和p-STAT3及下游靶基因Cyclin D1和Bcl-xL的表达。结果阴性对照组IGF-1R表达量(0.243±0.036)与空白对照组(0. 228±0.030)差异无统计学意义(P>0.05),IGF-1R-siRNA组IGF-1R表达量(0.071±0.010)低于空白对照组,差异有统计学意义(P<0.05)。IGF-1R-siRNA转染的OCM-1细胞IGF-1R的表达明显降低;与空白对照组比较,IGF-1R-siRNA组细胞活力显著降低,细胞凋亡率显著升高(均为P<0.05)。IGF-1R-siRNA组pJAK2、p-STAT3、Cyclin D1和Bcl-xL的蛋白表达均低于空白对照组,差异均有统计学意义(均为P<0. 05)。IGF-1R-siRNA+AG490组细胞活力低于IGF-1R-siRNA组,细胞凋亡率高于IGF-1R-siRNA组,差异均有统计学意义(均为P<0. 05)。IGF-1RsiRNA组p-JAK2、p-STAT3、Cyclin D1和Bcl-xL的蛋白表达均高于IGF-1R-siRNA+AG490组,差异均有统计学意义(均为P <0. 05)。结论下调IGF-1R基因表达可通过抑制STAT3信号通路降低CM细胞增殖并诱导细胞凋亡。Objective To investigate the inhibitory effect of IGF-1R gene expression on the proliferation and apoptosis of the choroidal melanoma cells and the STAT3 signaling pathway.Methods According to LipofectamineTM2000,IGF-1R siRNA was transfected into human choroidal melanoma cell OCM-1,and then the siRNA without interference and the cells added to the liposome were negative control group and blank control group,respectively,AG490 as an inhibitor of STAT3 signaling,the cells that have been transfected with 48 hours were cillected,and then cell viability and apoptosis rate were detected by CCK8 methods and flow cytometry;the expression of p-STAT3 p-JAK2,Cyclin D1 and Bcl-xL protein was detected by Western blot.Results There was no significant difference in the expression of IGF-1R between the negative control group(0.243±0.036)and the blank control group(0.228±0.030)(P>0.05).The expression of IGF-1R in the IGF-1R-siRNA group(0.071±0.010)was lower than that in the blank control group,the difference was statistically significant(P<0.05).The expression of IGF-1R in OCM-1 cells transfected with IGF-1R-siRNA was significantly decreased,and the cell viability and apoptosis rate were significantly decreased in the IGF-1R-siRNA group compared with the blank control group(all P<0.05).The protein expression of p-JAK2,p-STAT3,Cyclin D1 and Bcl-xL in the IGF-1R-siRNA group was lower than that in the blank control group,and the differences were statistically significant(all P<0.05).Cell viability of IGF-1R-siRNA+AG490 group was lower than that of IGF-1R-siRNA group,and apoptosis rate was higher than that of IGF-1R-siRNA group(all P<0.05).The protein expression of p-JAK2,p-STAT3,CyclinD1 and Bcl-xL in the IGF-1R-siRNA group was higher than that in the IGF-1R-siRNA+AG490 group,and the differences were statistically significant(all P<0.05).Conclusion The down-regulation of IGF-1R gene expression reduces proliferation and induce apoptosis of choroidal melanoma cells through inhibition STAT3 signaling pathway.

关 键 词：IGF-1R基因 脉络膜黑色素瘤 STAT3信号通路 增殖 凋亡 

分 类 号：R773[医药卫生—眼科]