A single drug chemotherapy fails to eliminate residual cancer cells due to the existence of the multidrug resistance （MDR）. In the present study, we aimed to develop a compound epirubicin plus quinine injection, to ...A single drug chemotherapy fails to eliminate residual cancer cells due to the existence of the multidrug resistance （MDR）. In the present study, we aimed to develop a compound epirubicin plus quinine injection, to characterize the efficacy in treatment of the drug-resistant breast cancer, and to reveal the involved mechanisms. The HPLC-UV methods were developed for quantifications, and the evaluations were performed on the drug-resistant human breast cancer MCF-7/adr cells using a high content screening system. Results demonstrated that the compound epirubicin plus quinine injection was able to effectively block the drug efflux, exhibiting an evidently overall efficacy in treatment of the resistant breast cancer cells by direct killing effect and by apoptosis-inducing effect. In the formulation, quinine played multiple roles in blocking drug efflux and in inducing the apoptosis of the resistant breast cancer cells. The apoptosis signaling pathways were associated with a cascade of reactions by activating Caspase family and by inhibiting Bcl-2 family. In conclusion, the present study preliminarily revealed the efficacy and mechanism of the compound epirubicin plus quinine formulation in treatment of the drug-resistant breast cancer, and offered a potential strategy to overcome drug resistance in cancer treatments.展开更多
基金National Natural Science Foundation of China(Grant No.81172991 and 81373343)
文摘A single drug chemotherapy fails to eliminate residual cancer cells due to the existence of the multidrug resistance （MDR）. In the present study, we aimed to develop a compound epirubicin plus quinine injection, to characterize the efficacy in treatment of the drug-resistant breast cancer, and to reveal the involved mechanisms. The HPLC-UV methods were developed for quantifications, and the evaluations were performed on the drug-resistant human breast cancer MCF-7/adr cells using a high content screening system. Results demonstrated that the compound epirubicin plus quinine injection was able to effectively block the drug efflux, exhibiting an evidently overall efficacy in treatment of the resistant breast cancer cells by direct killing effect and by apoptosis-inducing effect. In the formulation, quinine played multiple roles in blocking drug efflux and in inducing the apoptosis of the resistant breast cancer cells. The apoptosis signaling pathways were associated with a cascade of reactions by activating Caspase family and by inhibiting Bcl-2 family. In conclusion, the present study preliminarily revealed the efficacy and mechanism of the compound epirubicin plus quinine formulation in treatment of the drug-resistant breast cancer, and offered a potential strategy to overcome drug resistance in cancer treatments.
