摘要
目的分析信号转导子和激活子3(signal transducer and activator of transcription 3,STAT3)通过调控β-catenin信号通路对结直肠癌干细胞增殖和自噬的影响。方法结直肠癌细胞经培养、分选后获得结直肠癌干细胞,分为CCSC组、STAT3组、STAT3 ihibitor组、STAT3 inhibitor+Wnt/β-catenin-inhibitor组。检测各组细胞增殖率、凋亡率、增殖、凋亡、自噬相关蛋白、Wnt/β-catenin信号通路蛋白表达。结果癌组织CD133^(+)CD44^(+)细胞STAT3的表达量高于癌旁组织CD133^(-)CD44^(-)细胞(P<0.05)。与CCSC组比较,STAT3组STAT3、CyclinD1、Bcl-2、P62、Wnt2、β-catenin的表达水平、增殖率升高,凋亡率、Caspase-3、Bax、Beclin1的表达水平降低;与CCSC组、STAT3组比较,STAT3 ihibitor组、STAT3 inhibitor+Wnt/β-catenin-inhibitor组STAT3、CyclinD1、Bcl-2、P62、Wnt2、β-catenin的表达水平、增殖率降低,凋亡率、Caspase-3、Bax、Beclin1的表达水平升高(P<0.05);与STAT3 ihibitor组比较,STAT3 inhibitor+Wnt/β-catenin-inhibitor组STAT3、CyclinD1、Bcl-2、P62、Wnt2、β-catenin表达水平、增殖率降低,凋亡率、caspase-3、Bax、Beclin1的表达水平升高(P<0.05)。结论结直肠癌干细胞经下调STAT3干预后增殖率下降,凋亡率上升,自噬增强,其机制可能与Wnt/β-catenin信号通路被抑制有关。
Objective To investigate the effect of signal transducer and activator of transcription 3(STAT3)on the proliferation and autophagy of colorectal cancer stem cells.Methods The colorectal cancer stem cells were sorted out from colorectal cancer cells,and were categorized into 4 groups:CCSC,STAT3,STAT3 ihibitor,and STAT3 inhibitor+Wnt/β-catenin-inhibitor.The proliferation rate,apoptosis rate,and the expression levels of proteins related to cell proliferation,apoptosis,and autophagy,as well as Wnt/β-catenin signaling pathway proteins,were measured in each group.Results The expression levels of STAT3 in cancer tissues and CD133^(+)CD44^(+)cells were significantly higher than those in the adjacent tissues and CD133^(-)CD44^(-)cells(P<0.05).Compared to the CCSC group,the STAT3 group showed increased expression levels of STAT3,CyclinD1,Bcl-2,P62,Wnt2,andβ-catenin,as well as higher proliferation rates,while the apoptosis rate and the expression levels of Caspase-3,Bax,and Beclin1 were reduced.Compared to both the CCSC and STAT3 groups,the STAT3 ihibitor group and the STAT3 inhibitor+Wnt/β-catenin-inhibitor group showed decreased expression levels of STAT3,CyclinD1,Bcl-2,P62,Wnt2,andβ-catenin,as well as lower proliferation rates,while the apoptosis rate and the expression of Caspase-3,Bax,and Beclin1 were increased(P<0.05).Compared to the STAT3 ihibitor group,the STAT3 inhibitor+Wnt/β-catenin-inhibitor group showed decreased expression levels of STAT3,CyclinD1,Bcl-2,P62,Wnt2,andβ-catenin,as well as lower proliferation rates,while the apoptosis rate and the expression levels of Caspase-3,Bax,and Beclin1 were increased(P<0.05).Conclusion Downregulation of STAT3 inhibits the proliferation,and enhances the apoptosis and autophagy of colorectal cancer stem cells.The mechanism may be related to the inhibition of the Wnt/β-catenin signaling pathway.
作者
王林林
闫伟娇
WANG Linlin;Yan Weijiao(Department of Pharmacy,Handan Central Hospital,Handan,Hebei,056001,China)
出处
《医学分子生物学杂志》
2025年第5期494-499,共6页
Journal of Medical Molecular Biology
基金
邯郸市科学技术研究与发展计划项目(No.23422083002ZC)。
关键词
信号转导子和激活子3
Wnt/β-连环蛋白
结直肠癌
干细胞
增殖
自噬
signal transducer and activator of transcription 3
Wnt/β-catenin
colorectal cancer
stem cell
proliferation
autophagy
