Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (6): 438-447.DOI: 10.5246/jcps.2016.06.049

• Original articles • Previous Articles     Next Articles

Augmented efficacy and the mechanism of a combined use of daunorubicin with rofecoxib in treatment of triple-negative breast cancer

Yao Zhao, Jingying Zhang, Yingjie Hu, Jiashuan Wu, Yingzi Bu, Wanliang Lu*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2016-02-16 Revised:2016-03-25 Online:2016-06-29 Published:2016-03-30
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  • Supported by:
    National Natural Science Foundation of China (Grant No. 81373343) and the Key Grant of Beijing Natural Science Foundation (Grant No. 7131009).


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 daunorubicinand 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.

Key words: Daunorubicin, Rofecoxib, Triple-negative breast cancer, Apoptosis, Autophagy

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