siPGK1在调控黑色素瘤细胞对Vemurafenib敏感性中的作用及其机制

摘要

目的:研究磷酸甘油酸酯激酶1(PGK1)对BRAFv600E突变型恶性黑色素瘤(MM)对Vemurafenib (Zelboraf)敏感性的影响及其机制.方法:采用分子生物学、细胞生物学、药理学相关实验方法(MTT、Western blot、FCM、Colongenic)探讨:①PGK1以及Vemurafenib对MM细胞的存活增殖能力的影响;②通过siPGK1基因增加Vemurafenib药敏感性的机制.结果:①沉默PGK1基因后再给以BRAFv600E选择性抑制剂Vemurfenib,MM细胞系的存活率明显下降,并呈一定的剂量依赖性;②siPGK1增加MM细胞对Vemurafenib的药物敏感性与激活凋亡信号通路有关.结论:siPGK1通过激活凋亡信号通路增加MM细胞对Vemurafenib的药物敏感性,从而抑制细胞的存活和增殖能力.%Objective:To explore whether targeting phosphoglycerate kinase 1 (PGK1) can enhance the sensitivity of BRAFV600E mutation melanoma cells to vemurafenib.Methods:The methods of cell biology,molecular biology and pharmacology (MTT assay,Western blot,FCM,Colongenic assay) were used in this study.Results:① Silencing of PGKI expression increased the efficacy of vemurafenib in melanoma cells,as evidenced by greater killing in the tumor cells subjected to combined treatment of vemurafenib with siPGK1;②The mechanism of enhanced sensitivity of melanoma cells to vemurafenib was associated with activation of apoptotic signaling pathway.Conclusion:Targeting of PGK1 may represent a novel strategy of sensitizing melanoma cells to vemurafinib.