title: Salmonella VNP20009-mediated RNA interference of ABCB5 moderated chemoresistance of melanoma stem cell and suppressed tumor growth more potently.
abstract: Drug resistance remains an obstacle hindering the success of chemotherapy. Cancer stem cells (CSCs) have been recently found to confer resistance to chemotherapy. Therefore functional markers of CSCs should be discovered and specific therapies targeting these cells should be developed. In our investigation, a small population of B16F10 cells which was positive for ATP-binding cassette sub-family B member 5 (ABCB5) was isolated. This population displayed characteristics similar to those of CSCs and ABCB5 was identified to confer tumor growth and drug resistance in B16F10 cell line. Although targeting ABCB5 by small short interfering RNA delivered by VNP20009 failed to inhibit tumor growth, the combined treatment of VNP-shABCB5 and chemotherapy can act synergistically to delay tumor growth and enhance survival time in a primary B16F10 mice model. Results suggest that the combined treatment of VNP-shABCB5 and chemotherapy can improve the efficacy of chemotherapeutic drugs. Therefore, this combination therapy is of potential significance for melanoma treatment.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.|Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, Jiangsu, China.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.
authors.forename: Xiawei
authors.initials: X
authors.lastname: Cheng
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.
authors.forename: Yueyang
authors.initials: Y
authors.lastname: Lai
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Cao
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China.|Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, Jiangsu, China.|The State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, Jiangsu , China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis; D001428:Bacterial Vaccines / Q000494:pharmacology*; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004359:Drug Therapy, Combination; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D014407:Tumor Cells, Cultured
chemical_list: C573563:ABCB5 protein, mouse; D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D018906:Antineoplastic Agents, Alkylating; D001428:Bacterial Vaccines; D034741:RNA, Small Interfering; C465023:VNP 20009; D003520:Cyclophosphamide
keywords: ABCB5; anti-tumor; bacterial therapy; drug resistance; tumor initiating cells