文献类型：期刊文章

作　　者：赵曜[1,2] 张婧莹[1,2] 胡英杰[1,2] 吴佳栓[1,2] 卜英子[1,2] 吕万良[1,2]

机构地区：[1]北京大学医学部药学院分子药剂学与新释药系统北京市重点实验室 [2]天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》

基　　金：National Natural Science Foundation of China(Grant No.81373343);the Key Grant of Beijing Natural Science Foundation(Grant No.7131009)

年　　份：2016

卷　　号：25

期　　号：6

起止页码：438-447

语　　种：中文

收录情况：CAB、CAS、CSCD、CSCD2015_2016、DOAJ、EMBASE、IC、JST、SCOPUS、ZGKJHX、普通刊

摘　　要：Triple-negative breast cancer is the tumor that lacks expressions of estrogen receptor（ER）, progesterone receptor（PR） and human epidermal growth factor receptor-2（HER2）. A regular chemotherapy cannot eradicate triple-negative breast cancer. In the present study, we aimed to develop a combined use of daunorubicin and rofecoxib to treat triple-negative breast cancer, and reveal the underlying mechanisms. A gradient elution HPLC-UV method was developed for quantification, and the evaluations were performed on the triple-negative breast cancer MDA-MB-231 cells using a high content screening system. The results demonstrated that daunorubicin alone was insensitive to the triple negative breast cancer cells, while the combined use of daunorubicin and rofecoxib was able to effectively kill these triple-negative cancer cells, exhibiting a rofecoxib concentration-dependent manner. The mechanism revealed that the augmented anticancer efficacy was associated with direct killing effect, inducing apoptosis and inducing autophagy by the combination treatment. Besides, the apoptosis signaling pathways were correlated to a cascade of reactions by activating apoptotic enzyme caspase family and by suppressing anti-apoptotic gene expressed protein Bcl-2 family. In conclusion, this study provided a fundamental evidence for further developing the combined use of daunorubicin and rofecoxib formulation, hence offering a promising strategy for eradicating the triple negative breast cancer.

关 键 词：DAUNORUBICIN ROFECOXIB Triple-negative breast cancer  APOPTOSIS AUTOPHAGY

分 类 号：R737.9]