机构：[1]Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu四川省人民医院[2]Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
Inhibition of BRAF improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to BRAF inhibitor is inevitable, and the drug resistance mechanisms still remain to be elucidated. Here, BRAF(V600E) mutant cells A375 and SK-MEL-28 were chosen and treated with BRAF inhibitor vemurafenib, and the results showed that the ERK signaling pathway was blocked in these cells. Then, vemurafenib-resistant cells were constructed, and we found that drug resistance-related gene P-gp was overexpressed in the two cell lines. In addition, the histone acetylation was significantly increased on the P-gp promoter region, which suggested that the epigenetic modification participated in the P-gp overexpression. Furthermore, JQ1, a bromodomain inhibitor, was added to the vemurafenib-resistant cells and sensitizes the vemurafenib-induced melanoma cell apoptosis. In C57BL/6 mice intravenously injected with vemurafenib-resistant melanoma cells, cotreatment of vemurafenib and JQ1 also severely suppressed melanoma lung metastasis. Taken together, our findings may have important implications for the combined use of vemurafenib and JQ1 in the therapy for melanoma treatment. (C) 2018 The Author(s). Published by Wolters Kluwer Health, Inc.
基金：
General Program of the Health and Family Planning Commission of Sichuan Province [17PJ153]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|3 区医学
小类|2 区皮肤病学3 区医学：研究与实验4 区肿瘤学
最新[2023]版：
大类|4 区医学
小类|4 区皮肤病学4 区医学：研究与实验4 区肿瘤学
JCR分区：
出版当年[2018]版：
Q2DERMATOLOGYQ3MEDICINE, RESEARCH & EXPERIMENTALQ3ONCOLOGY
最新[2023]版：
Q3DERMATOLOGYQ3MEDICINE, RESEARCH & EXPERIMENTALQ4ONCOLOGY
第一作者机构：[1]Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu
通讯作者：
通讯机构：[1]Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu[*1]Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, No. 32 Western 2nd Section, 1st Circle Road, Chengdu 610072, Sichuan, China
推荐引用方式(GB/T 7714)：
Zhao Bei,Cheng Xiankui,Zhou Xiyuan.The BET-bromodomain inhibitor JQ1 mitigates vemurafenib drug resistance in melanoma[J].MELANOMA RESEARCH.2018,28(6):521-526.doi:10.1097/CMR.0000000000000497.
APA：
Zhao, Bei,Cheng, Xiankui&Zhou, Xiyuan.(2018).The BET-bromodomain inhibitor JQ1 mitigates vemurafenib drug resistance in melanoma.MELANOMA RESEARCH,28,(6)
MLA：
Zhao, Bei,et al."The BET-bromodomain inhibitor JQ1 mitigates vemurafenib drug resistance in melanoma".MELANOMA RESEARCH 28..6(2018):521-526
