摘要
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.
由于肿瘤的多药耐药性,传统的单药化疗无法根除残余癌细胞。本研究旨在研制一种复方表阿霉素奎宁注射液,评价其治疗耐药乳腺癌细胞的活性并揭示其机理。研究建立了用于药物定量的高效液相方法学,并应用高内涵分析系统对人耐药乳腺癌MCF--7/adr细胞系进行评价。结果显示,复方表阿霉素奎宁注射液可以显著抑制耐药性乳腺癌细胞的药物外排,通过直接杀伤和诱导凋亡的方式显著抑制耐药乳腺癌的增殖。在该复方注射液中,奎宁在抑制药物外排和诱导耐药乳腺癌细胞凋亡中起着重要作用。复方表阿霉素奎宁注射剂通过激活Caspase家族与抑制Bcl--2家族的蛋白表达等凋亡信号通路来诱导一系列凋亡反应。因此,本研究初步揭示了复方表阿霉素奎宁注射液抗耐药乳腺癌的活性与机制,从而为癌症治疗过程中克服多药耐药提供了一种备选的策略。
基金
National Natural Science Foundation of China(Grant No.81172991 and 81373343)
