BRD4沉默联合吉西他滨为治疗三阴性乳腺癌提供新的治疗方案  

BRD4 scilencing plus gemcitabine may be a novel therapy for triple-negative breast cancer

作　　者：陈玉丽[1] 朱勤伟[2] 隋晓梅[3] 王秀春[3] CHEN Yuli ZHU Qinwei SUI Xiaomei WANG Xiuchun(Weifang Medical University, Weifang 261041, Shandong Province, China The Traditional Chinese Medicine Hospital of Weifang, Weifang 261041, Shandong Province, China Department of Radiotherapy of the Affiliated Hospital of Weifang Medical University, Weifang 261042, Shandong Province, China)

机构地区：[1]潍坊医学院,山东潍坊261041 [2]潍坊市中医院,山东潍坊261041 [3]潍坊医学院附属医院放疗科,山东潍坊261042

出　　处：《中国癌症杂志》2016年第9期750-755,共6页China Oncology

基　　金：潍坊市卫生局科研立项项目(2014037)

摘　　要：背景与目的:乳腺癌是女性发病率最高的恶性肿瘤,其发病率和死亡率逐渐上升,特别是三阴性乳腺癌(triple-negative breast cancer,TNBC)缺乏有效的治疗靶点,死亡率更高。在以往的研究中,BRD4在多种肿瘤的进展中起到重要的作用。该研究旨在研究BRD4在耐吉西他滨的TNBC中所起到的作用,联合BRD4沉默和吉西他滨治疗TNBC的效果。方法:分别应用反转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)和蛋白[质]印迹法(Western blot)检测人乳腺癌细胞株MDA-MB-231和MDA-MB-453在吉西他滨治疗中表达变化。BRD4被sh BRD4沉默后,通过体内和体外实验验证BRD4在耐药的TNBC中所起到的作用。结果:在TNBC中,BRD4在吉西他滨诱导后表达量明显的升高(P<0.05)。沉默BRD4基因后,吉西他滨的半数抑制率明显降低,BRD4沉默联合吉西他滨使细胞的凋亡率明显升高(P<0.05);在体外实验中,BRD4沉默联合吉西他滨可以使肿瘤的生长速度明显降低(P<0.05)。结论:BRD4在耐药的TNBC中起到重要的作用,BRD4沉默联合吉西他滨为治疗TNBC提供新的治疗方法。Background and purpose： Breast cancer has the highest morbidity and mortality rate in women worldwide. Triple-negative breast cancer （TNBC） has no specific target and has low survival rate. Recent studies have verified BRD4 could promote tumor progression. This study aimed to detect the expression level of BRD4 in TNBC after treatment with gemcitabine, and to reveal the effect of BRD4 silencing plus gemcitabine as a treatment for TNBC. Methods： The expression of BRD4 in TNBC cell lines treated with gemcitabine was detected by reverse transcription PCR （RT-PCR） and Western blot. The effect of BRD4 silencing plus gemcitabine in TNBC was illustrated in vitro and in vivo. Results： The expression of BRD4 in TNBC was significantly increased after treatment with gemcitabine. In vitro, BRD4 knockdown significantly lowered the IC50 value. The apoptotic rate of TNBC was significantly increased in the BRD4 silencing plus gemcitabine group compared to the other. The growth rate of tumor in vivo was significantly lowered in the BRD4 silencing plus gemcitabine group. Conclusion： BRD4 may play an important role in the drug resistance to gemcitabine in TNBC. BRD4 silencing plus gemcitabine may be a novel treatment strategy for TNBC.

关 键 词：三阴性乳腺癌 BRD4 吉西他滨 

分 类 号：R737.9[医药卫生—肿瘤]