目的 探讨全反式维A酸(all-trans retinoic acid,ATRA)对胃癌干细胞相关基因CD133、Sox2及GSK3B表达的影响,为胃癌治疗提供新的切入点.方法 建立人胃癌裸鼠移植瘤模型,分为对照组、氟尿嘧啶组、ATRA组、氟尿嘧啶+ATRA组,采用ATRA腹腔注射,观察裸鼠一般状况,取出肿瘤组织,HE染色,检测各组胃癌细胞坏死情况;采用半定量反转录聚合酶链反应(RT-PCR)、实时定量PCR方法,分析检测CD133mRNA、Sox2mRNA及GSK3BmRNA基因表达,并通过免疫组化法检测CD133、Sox2及GSK3B蛋白表达.结果 与对照组相比较,氟尿嘧啶组、ATRA组、氟尿嘧啶+ATRA组肿瘤体积缩小,差异有统计学意义(P＜0.05);氟尿嘧啶组、ATRA组、氟尿嘧啶+ATRA组高表达CD133、Sox2干细胞相关因子;ATRA组、氟尿嘧啶+ATRA组高表达GSK3B,差异有统计学意义(P＜0.05).结论 ATRA作用后胃癌干细胞标志物CD133、Sox2、GSK3B表达增加;CD133、Sox2、GSK3B表达增加可以抑制肿瘤细胞生长;ATRA老药新用对胃癌的治疗预后有一定的作用.%Objective To investigate tbe effect of all-trans retinoic acid (ATRA) on related genes CD133,Sox2 and GSK3B of gastric cancer stem cells in order to find a new starting point for the treatment of gastric cancer.Methods Human gastric cancer xenografts in nude mice were divided into control group,5-FU group,ATRA group and 5-FU + ATRA group.After intraperitoneal injection of ATRA,the general condition of nude mice were observed before the tumor-bearing mice were sacrificed to remove the tumor tissue.HE staining was used to detect gastric cancer cell necrosis of the tissue.The expression of CD133mRNA,Sox2mRNA and GSK3BmRNA was detected using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR analysis while immunohistochemistry was adopted to detect the expression of CD133,Sox2 protein and GSK3B.Results Compared with the control group,the tumor shrank in 5-Fu group,ATRA group,and 5-Fu + ATRA group.The difference was significant (P ＜ 0.05).The expressions of CD133,Sox2 stem cell-related factors were high in 5-Fu group,ATRA group,and 5-Fu + ATRA group.However,there was significant difference in GSK3B expression between ATRA group and 5-Fu + ATRA group,(P ＜0.05).Conclusions Ater the administration of ATRA,gastric cancer stem cell markers,such as CD133 and Sox2,have a higher expression.The increased expression of CD133,Sox2 and GSK3B might inhibit the growth of tumor cells.The new use of ATRA can contribute to the prognosis of gastric cancer.
展开▼
