Efficacy and mechanism of antiresistant vinorelbine liposomes in treating resistant breast cancer cells

doi:10.5246/jcps.2016.07.054

Abstract

Abstract:

Among the comprehensive treatment strategies of breast cancer, chemotherapy plays a crucial role in eliminating cancer cells. However, multidrug resistance is one of the major obstacles to successful treatment. The objectives of this study were to construct an antiresistant vinorelbine liposomes and to demonstrate the efficacy and mechanism for treating resistant breast cancer cells. The study was performed using breast cancer MCF-7/adr cells. The antiresistant vinorelbine liposomes were modified with tamoxifen and dequalinium. The average particle size of antiresistant vinorelbine liposomes were approximately 100 nm, and they showed a robust overall anticancer efficacy by direct killing and by apoptosis induction. The mechanisms were associated with increased cellular uptake, decreased ABCB1 and ABCC10 transporters, and targeting to mitochondria. The apoptosis signaling pathways were ralated to activiated caspases (8, 9, 3), induced release of cytochrome c from mitochondria, activated Bax, inhibited Mcl-1, and generation of ROS. The new antiresistant vinorelbine liposomes could be a useful formulation deserving further development, and the present study provides a potential strategy for circumventing drug resistance in breast cancer.

Key words: Antiresistant vinorelbine liposomes, Mitochondrial targeting, Apoptosis signaling pathways, Efficacy, Resistant breast cancer

CLC Number:

R943

Supporting:

Hongjun Xie, Lei Liu, Fan Zeng, Limin Mu, Yao Zhao, Yan Yan, Yingjie Hu, Jiashuan Wu, Yingzi Bu, Jingying Zhang, Wanliang Lu. Efficacy and mechanism of antiresistant vinorelbine liposomes in treating resistant breast cancer cells[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(7): 489-501.

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