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

目的：研究磷酸甘油酸酯激酶1（PGK1）对BRAF^V600E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BRAF^V600E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。

Silencing of PKG1 expression enhances the efficacy of vemurafenib against melanoma cell

Objective: To explore whether targeting phosphoglycerate kinase 1 (PGK1) can enhance the sensitivity of BRAF^V600E 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 PGK1 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.