title: Data showing the circumvention of oxaliplatin resistance by vatalanib in colon cancer.
abstract: We have recently reported that vatalanib, an orally active small molecule multi-tyrosine kinase inhibitor (Hess-Stumpp et al., 2005 [1]), can sensitize multidrug resistant (MDR) colon cancer cells to chemotherapy under hypoxia by inhibiting two MDR transporters ABCB1 and ABCG2 (To et al., 2015 [2]). This data article describes the possible circumvention of resistance to specifically platinum (Pt)-based anticancer drugs by vatalanib via inhibition of two other efflux transporters ABCC2 and ATP7A. Data from the flow cytometric transporter efflux assay showed specific inhibition of ABCC2 activity by vatalanib in stable transfected cells and ABCC2-overexpressing oxaliplatin-resistant colon cancer cells HCT116/Oxa. We also performed the transporter ABCC2 ATPase assay and showed an increase in ATP hydrolysis by ABCC2 in the presence of vatalanib. ATP7A mRNA expression was also shown to be upregulated in HCT116/Oxa cells. Vatalanib was shown to suppress this upregulated ATP7A expression. Data from the cellular Pt accumulation assay showed a lower Pt accumulation in HCT116/Oxa cells than the parental sensitive HCT116 cells. Vatalanib was shown to increase cellular Pt accumulation in a concentration-dependent manner. Combination of oxaliplatin and vatalanib was shown to restore the suppressed apoptosis in HCT116/Oxa cells.
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kenneth K W
authors.initials: KK
authors.lastname: To
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Poon
authors.affiliation: School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Fu
keywords: Chemoresistance; Oxaliplatin; Platinum drugs; Tyrosine kinase inhibitor; Vatalanib