Application of functional vincristine plus dasatinib liposomes to deletion of vasculogenic mimicry channels in triple-negative breast cancer

• Published in: Oncotarget Vol. 6; no. 34; pp. 36625 - 36642
• Main Authors: Zeng, Fan, Ju, Rui-Jun, Liu, Lei, Xie, Hong-Jun, Mu, Li-Min, Zhao, Yao, Yan, Yan, Hu, Ying-Jie, Wu, Jia-Shuan, Lu, Wan-Liang
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 03.11.2015
• Subjects: Animals; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Apoptosis - drug effects; Cell Line, Tumor; Dasatinib - administration & dosage; Disease Models, Animal; Female; Humans; Liposomes - administration & dosage; Mice; Mice, Inbred BALB C; Mice, Nude; Random Allocation; Research Paper; Triple Negative Breast Neoplasms - blood supply; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Vincristine - administration & dosage; Xenograft Model Antitumor Assays; functional liposome; triple-negative breast cancer; dasatinib; vincristine; vasculogenic mimicry channel
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.5382

Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while the residual cancer cells readily form the vasculogenic mimicry (VM) channels, which lead to the relapse of cancer after treatment. In this study, the functional vincristine plus dasatinib liposomes, modified by a targeting molecule DSPE-PEG2000-c(RGDyK), were fabricated to address this issue. The investigations were performed on TNBC MDA-MB-231 cells and MDA-MB-231 xenografts in nude mice. The liposomes exhibited the superior performances in the following aspects: the enhancement of cellular uptake via targeted action; the induction of apoptosis via activation of caspase 8, 9, and 3, increased expression of Bax, decreased expression of Mcl-1, and generation of reactive oxygen species (ROS); and the deletion of VM channels via inhibitions on the VM channel indicators, which consisted of vascular endothelial-cadherin (VE-Cad), focal adhesion kinase (FAK), phosphatidylinositide 3-kinase (PI3K), and matrix metallopeptidases (MMP-2, and MMP-9). Furthermore, the liposomes displayed the prolonged circulation time in the blood, the increased accumulation in tumor tissue, and the improved therapeutic efficacy along with deletion of VM channels in the TNBC-bearing mice. In conclusion, the nanostructured functional drug-loaded liposomes may provide a promising strategy for the treatment of invasive TNBC along with deletion of VM channels.