A potential target associated with both cancer and cancer stem cells: a combination therapy for eradication of breast cancer using vinorelbine stealthy liposomes plus parthenolide stealthy liposomes.
The cancer stem cells play a critical role in both initiation and relapse of the cancers as they are resistant to the most of cytotoxic agents and able to proliferate indefinitely. Vinorelbine stealthy liposomes and parthenolide stealthy liposomes were developed for providing beneficial pharmacological properties and to eradicate cancer stem cells and non-stem cancer cells together by a combination therapy. Cytotoxicity and cancer stem-like cells (side population, SP) identification were performed on human breast cancer cell lines MCF-7 and MDA-MB-231. SP cells were further sorted from MCF-7 cells and characterized. Inhibitory effect was evaluated on the sorted SP and non-SP cells. Antitumor activity was evaluated on MCF-7 xenografts in nude mice. SP cells were identified with a higher percentage in MCF-7 cells (3.8%) and lower in MDA-MB-231 cells (0.6%). Both vinorelbine and parthenolide inhibited the proliferation in MCF-7 and MDA-MB-231 cells. As compared to non-SP cells, inhibitory effect of vinorelbine in the SP cells was lower while a robust inhibitory effect was observed when applying vinorelbine in combination with parthenolide. In the MCF-7 xenografts, stealthy liposomal vinorelbine plus stealthy liposomal parthenolide produced a full inhibitory effect. This combination therapy may provide a potential strategy for eradication of breast cancer by targeting cancer together with cancer stem cells.
Liu
Yang
Y
State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Lu
Wan-Liang
WL
Guo
Jia
J
Du
Ju
J
Li
Ting
T
Wu
Jin-Wei
JW
Wang
Gui-Ling
GL
Wang
Jian-Cheng
JC
Zhang
Xuan
X
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D008081:Liposomes; D012717:Sesquiterpenes; C002669:parthenolide; D014747:Vinblastine; D000077235:Vinorelbine