Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells
| Autor: | Ben, Doherty, Denise, Lawlor, Jean-Pierre, Gillet, Michael, Gottesman, John J, O'Leary, Britta, Stordal |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adenosine Triphosphatases
ATP Binding Cassette Transporter Subfamily B Reverse Transcriptase Polymerase Chain Reaction Blotting Western Uterine Cervical Neoplasms Antineoplastic Agents Real-Time Polymerase Chain Reaction Glutathione Gene Expression Regulation Neoplastic Glutathione S-Transferase pi Copper-Transporting ATPases Drug Resistance Neoplasm Tumor Cells Cultured Humans Metabolomics Female ATP Binding Cassette Transporter Subfamily B Member 1 RNA Messenger Cisplatin Cation Transport Proteins Cell Proliferation Glutathione Transferase |
| Zdroj: | Anticancer research. 34(1) |
| ISSN: | 1791-7530 |
| Popis: | 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.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.KB-8-5-11 cells were sensitive to CuSO4 and the glutathione inhibitor buthionine sulphoximine. Expression of ATPase, Cu(2+) 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.KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|