延龄草苷通过降低SCD1表达促进结直肠癌细胞凋亡  

Diosgenin glucoside promotes apoptosis of colorectal cancer cells by decreasing expression of SCD1

作　　者：万星 张芳[3] 李奉 李志贵 周黎明 WAN Xing;ZHANG Fang;LI Feng;LI Zhigui;ZHOU Liming(Department of Pharmacology,Health Science Center,Hubei Minzu University,Enshi 445000,China;Department of Pharmacology,Sichuan University West China School of Basic Medical Sciences&Forensic Medicine,Chengdu 610044,China;Department of Oncology,The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi 445099,China;Department of General Surgery,Colorectal Cancer Center,Sichuan University West China Hospital,Chengdu 610041,China)

机构地区：[1]湖北民族大学医学部药理教研室,湖北恩施445000 [2]四川大学基础医学与法医学院药理教研室,四川成都610044 [3]恩施土家族苗族自治州中心医院肿瘤科,湖北恩施445099 [4]四川大学华西医院结直肠肿瘤中心,四川成都610041

出　　处：《中国病理生理杂志》2025年第1期97-103,共7页Chinese Journal of Pathophysiology

基　　金：四川省科技计划项目重点研发项目(No.2022YFS0337)。

摘　　要：目的:探讨硬脂酰辅酶A去饱和酶1(stearoyl-CoA desaturase 1,SCD1)在结直肠癌中的临床意义及延龄草苷影响结直肠癌细胞增殖的作用及机制。方法:采用qPCR和Western blot检测SCD1在临床患者结直肠癌组织中的表达,并分析其与临床特征的关系;CCK-8检测不同浓度延龄草苷对SW620和HCT116细胞活力的影响;细胞集落形成实验分析不同浓度延龄草苷对上述细胞增殖能力的影响;qPCR和Western blot检测其对凋亡基因以及SCD1的影响;分子对接技术分析延龄草苷与SCD1的结合部位及结合能。结果:SCD1的mRNA和蛋白在结直肠癌中的表达较癌旁组织增高,mRNA高表达的阳性率为88%,且其表达与结直肠癌种类和临床分期相关:与结肠癌相比,SCD1在直肠癌中具有更高的表达量,且随着临床分期加重,SCD1的表达随之升高;不同浓度延龄草苷一方面量效依赖地降低SW620和HCT116细胞的活力、抑制细胞集落形成,增加促凋亡蛋白caspase-3和Bax的mRNA和蛋白表达,降低抗凋亡蛋白Bcl-2的mRNA和蛋白表达,另一方面通过氢键和共轭键与SCD1结合降低其mRNA和蛋白表达,该结合能高达−7.7 kcal/mol。结论:SCD1是与结直肠癌种类和临床分期密切相关的蛋白;延龄草苷降低结直肠癌细胞活力、抑制增殖的机制可能是与SCD1结合降低其表达从而促进细胞凋亡相关。AIM:To explore the clinical significance of stearoyl-CoA desaturase 1(SCD1)in colorectal cancer and to evaluate the effects and mechanisms of diosgenin glucoside on the proliferation of colorectal cancer cells.METHODS:The expression of SCD1 in colorectal cancer tissues was assessed using qPCR and Western blot,and its correlation with clinical features was analyzed.The impact of diosgenin glucoside on the viability of SW620 and HCT116 cells was measured using the CCK-8 assay,and the proliferation was further investigated through cell cloning experiments.Additionally,the effects of diosgenin glucoside on apoptosis-related genes and SCD1 were evaluated by qPCR and Western blot.Molecular docking was employed to analyze the binding site and binding energy between diosgenin glucoside and SCD1.RESULTS:(1)Both SCD1 mRNA and protein were highly expressed in colorectal cancer tissues,with an 88%positive rate.And SCD1 mRNA expression correlated with cancer type and clinical stage.(2)Diosgenin glucoside decreased the viability and cloning ability of SW620 and HCT116 cells in a dose-dependent manner.(3)Diosgenin glucoside upregulated the mRNA and protein expression of pro-apoptotic proteins caspase-3 and Bax in a dose-dependent man ner,while it downregulated the mRNA and protein expression of the anti-apoptotic protein Bcl-2.(4)Diosgenin glucoside reduced the mRNA and protein expression of SCD1 in a dose-dependent manner and bound to SCD1 via hydrogen and conjugated bonds with a binding energy of−7.7 kcal/mol.CONCLUSION:(1)SCD1 is closely associated with the type and clinical stage of colorectal cancer.(2)The reduction in viability and proliferation of colorectal cancer cells by diosgenin glucoside may be attributed to its binding to SCD1,which lowers its expression and promotes apoptosis.

关 键 词：延龄草苷 结直肠癌 硬脂酰辅酶A去饱和酶1 细胞凋亡 

分 类 号：R363.2[医药卫生—病理学] R966[医药卫生—基础医学] R735.2