TY - JOUR T1 - Collateral Sensitivity to Cisplatin in KB-8-5-11 Drug-resistant Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 503 LP - 507 VL - 34 IS - 1 AU - BEN DOHERTY AU - DENISE LAWLOR AU - JEAN-PIERRE GILLET AU - MICHAEL GOTTESMAN AU - JOHN J. O'LEARY AU - BRITTA STORDAL Y1 - 2014/01/01 UR - http://ar.iiarjournals.org/content/34/1/503.abstract N2 - Background: KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer. Materials and Methods: A Taqman low-density array was used to characterize the expression of 380 genes previously associated with chemoresistance. Identified pathways were further analyzed using cytotoxicity assays, metabolomics and western blots. Results: KB-8-5-11 cells were sensitive to CuSO4 and the glutathione inhibitor buthionine sulphoximine. Expression of ATPase, Cu2+ transporting alpha (ATP7A) and ATP7B were decreased at the protein and gene levels respectively in KB-8-5-11. KB-8-5-11 had decreased gene expression of glutathione S-transferase pi 1 (GSTP1), GSTA4 and GSTK1. Cisplatin treatment significantly lowered total cellular glutathione in parental KB-3-1 cells. Glutathione also tended to be lower in KB-8-5-11 cells compared to KB-3-1 cells. Conclusion: KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype. ER -