Salmonella VNP20009-mediated RNA interference of ABCB5 moderated chemoresistance of melanoma stem cell and suppressed tumor growth more potently

Xiaoxin Zhang; Xiawei Cheng; Yueyang Lai; Yuqiang Zhou; Wenmin Cao; Zi-Chun Hua

doi:10.18632/oncotarget.7496

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Research Papers:

Salmonella VNP20009-mediated RNA interference of ABCB5 moderated chemoresistance of melanoma stem cell and suppressed tumor growth more potently

Xiaoxin Zhang, Xiawei Cheng, Yueyang Lai, Yuqiang Zhou, Wenmin Cao and Zi-Chun Hua _

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Oncotarget. 2016; 7:14940-14950. https://doi.org/10.18632/oncotarget.7496

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Abstract

Xiaoxin Zhang1,2, Xiawei Cheng1, Yueyang Lai1, Yuqiang Zhou1, Wenmin Cao1, Zi-Chun Hua1,2,3

1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, Jiangsu, China

2Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, Jiangsu, China

3The State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China

Correspondence to:

Zi-Chun Hua, e-mail: [email protected]

Keywords: bacterial therapy, ABCB5, tumor initiating cells, drug resistance, antitumor

Received: September 01, 2015 Accepted: January 19, 2016 Published: February 19, 2016

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.

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Research Papers:

Salmonella VNP20009-mediated RNA interference of ABCB5 moderated chemoresistance of melanoma stem cell and suppressed tumor growth more potently

Abstract