缺氧诱导因子-1α调节视网膜母细胞瘤的作用  

Role of hypoxia-inducible factor-1αin regulating retinoblastoma

作　　者：张丽红[1] 李威威[1] 孙璐 李世强[1] 武宗楠 Zhang Lihong;Li Weiwei;Sun Lu;Li Shiqiang;Wu Zongnan(No.3 Department of Ophthalmology,Baoding NO.1 Central Hospital,Baoding 071000;Department of Ophthalmology,Peking Union Medical College Hospital,Beijing 100730,China)

机构地区：[1]保定市第一中心医院眼三科,保定071000 [2]北京协和医院眼科,北京100730

出　　处：《解剖学杂志》2024年第5期415-419,435,共6页Chinese Journal of Anatomy

基　　金：河北省科技计划项目(20557708K)。

摘　　要：目的:分析缺氧诱导因子-1α(HIF-1α)调节视网膜母细胞瘤的干样特性、氧化应激和裸鼠成瘤等作用。方法:设计3组干扰HIF-1α的shRNA转染视网膜母细胞瘤(WERI-Rb-1)细胞株(HIF-1α-shRNA1组、HIF-1α-shRNA2组和HIF-1α-shRNA3组),选择干扰效果最好的shRNA进行后续研究;将WERI-Rb-1细胞分为对照组、shRNANC组和HIF-1α-shRNA组;检测各组细胞增殖能力,氧化应激标志物超氧化物歧化酶(SOD)、丙二醛(MDA),谷胱甘肽过氧化物酶(GSH-px)含量,肿瘤细胞成球情况和干细胞标记物(Oct4、Nanog和ABCG2)蛋白表达情况。结果:对照组和shRNA-NC组所有指标差异均无统计学意义。相比于HIF-1α-shRNA1组和HIF-1α-shRNA2组,HIF-1α-shRNA3组HIF-1αmRNA及蛋白相对表达水平最低。相比于shRNA-NC组,HIF-1α-shRNA3组细胞增殖数量明显减少。相比于shRNA-NC组,HIF-1α-shRNA3组瘤体直径变小,质量变轻,成球数量减少。相比于shRNA-NC组,HIF-1α-shRNA3组Oct4、Nanog和ABCG2蛋白水平相对表达量降低。相比于shRNA-NC组,HIF-1α-shRNA3组MDA和GSH-px含量增加,SOD含量明显减少。结论:干扰HIF-1α基因表达,抑制视网膜母细胞增殖,影响细胞抗氧化能力及干细胞标记蛋白表达,从而抑制肿瘤生长。Objective:To analyze the role of hypoxia inducible factor-1α(HIF-1α)in regulating stem cell-like characteristics,oxidative stress,and tumor formation of retinoblastoma(RB)in nude mice.Methods:Three groups of shRNA transfected RB with HIF-1αinterfere(WERI-Rb-1)cell lines were designed,and the shRNA with the best interference effect was selected for follow-up research.WERI-Rb-1 cells were divided into Control group,shRNA-NC group,and HIF-1α-shRNA group.The ability of cells proliferation,contents of oxidative stress markers[superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-px)],spheroidization of tumor cells and protein expression of stem cell markers(Oct4,Nanog,ABCG2)in each group were detected.Results:There was no significant difference in all indexes between the Control group and shRNA-NC group.Compared with the HIF-1α-shRNA1 group and HIF-1α-shRNA2 group,the relative expression levels of HIF-1αmRNA and protein were the lowest in the HIF-1α-shRNA3 group.Compared with the shRNA-NC group,the number of proliferation cells was significantly less in the HIF-1α-shRNA3 group,with reduced diameter of tumors,lighter mass,and less spheroidization cells.Compared with the shRNA-NC group,the relative expression levels of Oct4,Nanog and ABCG2 proteins were significantly lower,contents of MDA and GSH-px were significantly higher,and SOD content was significantly lower in the HIF-1α-shRNA3 group.Conclusion:Interfering with the expression of HIF-1αgene can inhibit RB proliferation,affect antioxidant capacity of cells and the expression of stem cell marker proteins,thereby inhibiting tumor growth.

关 键 词：缺氧诱导因子-1Α 视网膜母细胞瘤 氧化应激 成瘤 裸鼠 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]