Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells

Article

Doherty, B., Lawlor, D., Gillet, J., Gottesman, M., O'Leary, J. and Stordal, B. 2014. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells. Anticancer Research. 34 (1), pp. 503-507.
TypeArticle
TitleCollateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells
AuthorsDoherty, B., Lawlor, D., Gillet, J., Gottesman, M., O'Leary, J. and Stordal, B.
Abstract

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, 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.
CONCLUSION: KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype.

KeywordsCisplatin; paclitaxel; drug resistance; collateral sensitivity; cervical cancer; KB-8-5-11 cells
Research GroupBiomarkers for Cancer group
PublisherInternational Institute of Anticancer Research (IIAR)
JournalAnticancer Research
ISSN0250-7005
Electronic1791-7530
Publication dates
Online08 Jan 2014
Print31 Jan 2014
Publication process dates
Deposited13 Mar 2015
Accepted27 Nov 2013
Output statusPublished
Web address (URL)http://ar.iiarjournals.org/content/34/1/503.abstract
PubMed ID24403508
Web of Science identifierWOS:000329765400013
LanguageEnglish
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