alexa Pharmacogenomic Analysis Identifies Increased Efficacy of Oxaliplatin in ABCB1 Overexpressing Tumors
ISSN: 2153-0645

Journal of Pharmacogenomics & Pharmacoproteomics
Open Access

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Research Article

Pharmacogenomic Analysis Identifies Increased Efficacy of Oxaliplatin in ABCB1 Overexpressing Tumors

Anh-Nhan Pham1, Mingju Cao2, Paul E. Blower3, Moses S. Chow1and Ying Huang1*

1Center for the Advancement of Drug Research and Evaluation, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA

2College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA

3Program of Pharmacogenomics, Department of Pharmacology, Comprehensive Cancer Center, College of Medicine and Public Health, Ohio State University, Columbus, Ohio 43210, USA

*Corresponding Author:
Ying Huang
Department of Pharmaceutical Sciences, College of Pharmacy
Western University of Health Sciences, Pomona, CA 91766, USA
Tel: +1-909-469-5220
Fax: +1-909-469-5600
E-Mail: [email protected]

Received date: June 06, 2012; Accepted date: June 28, 2012; Published date: July 02, 2012

Citation: Pham AN, Cao M, Blower PE, Chow MS, Huang Y (2012) Pharmacogenomic Analysis Identifies Increased Efficacy of Oxaliplatin in ABCB1 Overexpressing Tumors. J Pharmacogenomics Pharmacoproteomics 3:110. doi: 10.4172/2153-0645.1000110

Copyright: © 2012 Pham AN, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Oxaliplatin is a platinum-class drug used for advanced colorectal cancer, which is still incurable because ofdrug resistance. We applied a pharmacogenomic approach to correlate mRNA expression profiles of transportergenes and growth inhibitory potency of oxaliplatin in NCI-60. Expression of ABCB1 (MDR1, P-glycoprotein) genepositively correlated with anticancer activity of oxaliplatin, but not with cisplatin and other platinum analogs. Thiscorrelation suggests that cell lines with higher ABCB1 expression were more sensitive to oxaliplatin. MDR1 inhibitorscyclosporine A, PSC 833 or verapamil significantly reduced the sensitivity to oxaliplatin in ABCB1 overexpressingovarian cancer cell line NCI/ADR-RES and colon cancer cell line HCT-15, whereas increased the sensitivity to MDR1 substrate drugs. These results provide evidence that the effect of oxaliplatin may be selective for tumor cells with high level of ABCB1 and overcome drug resistance. Such finding may provide an exciting prospect for future individualization of oxaliplatin-based cancer therapy.

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