【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。更多还原

【Abstract】 AIM: To explore the clinical significance of stearoyl-CoA desaturase 1(SCD1) in colorectal can?cer 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 cor?relation 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. Ad?ditionally, 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 de?creased the viability and cloning ability of SW620 and HCT116 cells in a dose-dependent manner.(3) Diosgenin gluco?side 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 con?jugated 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.更多还原