ATP-柠檬酸裂解酶在黑素瘤维罗非尼治疗抵抗中的作用机制研究  

The Role of ACLY in Vemurafenib Treatment Resistance in Melanoma and the Underlying Mechanism

作　　者：田阳子[1] 张倩[1] 易秀莉[1] 王慧娜 王思佳 郭伟楠[1] TIAN Yang-zi;ZHANG Qian;YI Xiu-li;WANG Hui-na;WANG Si-jia;GUO Wei-nan(Department of Dermatology,Xijing Hospital,Fourth Military Medical University,Xi'an,Shaanxi,710032,China)

机构地区：[1]第四军医大学西京皮肤医院,陕西西安710032

出　　处：《现代生物医学进展》2020年第1期30-34,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81625020,81402261)。

摘　　要：目的:探讨ATP-柠檬酸裂解酶(ATP-citrate lyase,ACLY)在黑素瘤维罗非尼治疗抵抗中的作用及其可能机制。方法:通过Western blot实验检测5μM维罗非尼处理前后黑素瘤细胞中ACLY的表达水平,采用shRNA干涉黑素瘤细胞中ACLY的表达后再给予5μM维罗非尼处理,通过流式细胞术检测细胞凋亡水平;通过Western blot实验检测黑素瘤特异性转录因子MITF的表达水平,以及抗凋亡蛋白BCL-2和促凋亡蛋白BAX的表达水平。结果:1)维罗非尼处理后黑素瘤细胞ACLY的表达水平较处理前明显升高;2)沉默ACLY可以显著增加维罗非尼处理后黑素瘤细胞的凋亡水平;3)在维罗非尼处理下,沉默ACLY可以导致MITF和BCL-2表达水平较对照组显著降低,BAX表达水平升高。结论:ACLY表达水平升高参与了黑素瘤维罗非尼治疗抵抗,可能与其调控MITF表达的作用有关。Objective:To investigate the role of ATP-citrate lyase(ACLY)in Vemurafenib treatment resistance in melanoma and the possible mechanism.Method(s):Western blot was used to detect the protein expression of ACLY in melanoma cells before and after the treatment of 5μM Vemurafenib.Flow cytometry analysis was used to examine cell apoptosis of melanoma cell with or without the knockdown of ACLY after 5μM Vemurafenib treatment.The expression levels of melanocytic-lineage specific transcriptional factor MITF(microphthalmia-associated transcription factor),and anti-apoptotic BCL-2 and pro-apoptotic BAX were detected by Western blot.Result(s):1)Vemurafenib treatment increased the expression of ACLY in melanoma cells;2)The knockdown of ACLY could significantly increase the apoptosis of melanoma cells induced by Vemurafenib;3)Under Vemurafenib treatment,ACLY expression deficiency resulted in the down-regulation of MITF and BCL-2,and the up-regulation of BAX.Conclusion(s):ACLY is involved in the Vemurafenib treatment resistance in melanoma,and this effect may be related to the regulation of MITF expression by ACLY.

关 键 词：ATP-柠檬酸裂解酶 黑素瘤 维罗非尼 

分 类 号：R-33[医药卫生] R739.5