Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells.

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Plasencia C, Martinez-Balibrea E, Martinez-Cardus A, Quinn DI, Abad A, Neamati N

Expression analysis of genes involved in oxaliplatin response and development of oxaliplatin-resistant HT29 colon cancer cells.

Int J Oncol. 2006 Jul;29(1):225-35.

PubMed ID

16773204 [ View in PubMed

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Abstract

The interrelationship between platinum resistance and clinical response is not well established. The purpose of this study is to evaluate the expression of 14 genes involved in platinum resistance in a colon cancer cell line (HT29) and its oxaliplatin (OXA)-resistant sublines. Resistant cells exhibited lower expression of many of these genes suggesting that several pathways may be implicated in OXA resistance. Particularly, OXA resistance is accompanied by defects in drug uptake (downregulation of the hCTR1 transporter) and enhanced DNA repair (upregulation of the XPD gene). Our data also confirmed that copper transporters and chaperones are involved in OXA resistance in colorectal cancer cells as evidenced by the overexpression of ATP7A and CCS in response to OXA exposure. Moreover, increased CCS expression suggests a role for SOD1 in OXA detoxification. Whereas exposure to OXA in HT29 induced significant changes in expression of many of the genes analyzed, only ATP7A, XPD and SRPK1 gene expression was increased in OXA-treated HTOXAR3 resistant cells. To our knowledge, this is the first report of implicating SRPK1 in OXA resistance. This study provides the basis for further evaluation of these putative markers of OXA response and resistance in colorectal cancer patients who are candidates for treatment with OXA.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Oxaliplatin	Superoxide dismutase [Cu-Zn]	Protein	Humans	No	Substrate	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Oxaliplatin	Approved Investigational	ATP7A	538	upregulated	oxaliplatin results in increased expression of ATP7A mRNA	Xq21.1
Oxaliplatin	Approved Investigational	ATP7B	540	downregulated	oxaliplatin results in decreased expression of ATP7B mRNA	13q14.3
Oxaliplatin	Approved Investigational	CCS	9973	upregulated	oxaliplatin results in increased expression of CCS mRNA	11q13.2
Oxaliplatin	Approved Investigational	ERCC1	2067	upregulated	oxaliplatin results in increased expression of ERCC1 mRNA	19q13.32
Oxaliplatin	Approved Investigational	ERCC2	2068	upregulated	oxaliplatin results in increased expression of ERCC2 mRNA	19q13.32
Oxaliplatin	Approved Investigational	GSTP1	2950	upregulated	oxaliplatin results in increased expression of GSTP1 mRNA	11q13.2
Oxaliplatin	Approved Investigational	MT2A	4502	downregulated	oxaliplatin results in decreased expression of MT2A mRNA	16q13
Oxaliplatin	Approved Investigational	SRPK1	6732	upregulated	oxaliplatin results in increased expression of SRPK1 mRNA	6p21.31