Description:
<jats:title>Abstract</jats:title>
<jats:p>Purpose: The mechanism of Oxaliplatin (OHP) resistance is partly understood and no molecular marker for prediction of the sensitivity is available in clinic. We analyzed OHP resistant clones to establish the molecular marker for OHP sensitivity in colorectal cancer.</jats:p>
<jats:p>Experimental design: We established several OHP-resistant clones from human colon cancer cell lines, DLD1 and HCT116. Then we assayed IC50 of OHP- resistant clones against OHP, 5-FU, and CPT-11. We measured gene expression profiling by microarray analysis and gene mutations by exome sequencing. Based on these results, we selected candidate genes associated with OHP sensitivity, which had gene mutations with significant change of gene expression. To validate the results, we assessed the gene expression of candidate genes in colorectal cancer patients.</jats:p>
<jats:p>Results: All OHP-resistant clones derived from HCT116 were also resistant against 5-FU and CPT-11, although all OHP-resistant clones derived from DLD1 were still sensitive against 5-FU and CPT-11. Microarray analysis and exon sequencing indicated gene mutations in SMAD7 and IRF9 with amplified gene expression were candidate molecular markers for multidrug resistance in OHP-resistant clones derived from HCT116, although the gene expression in tumors of these genes were lower than normal mucosa in most of colorectal cancer patients.</jats:p>
<jats:p>Conclusions: The mechanisms of OHP resistance were different between OHP-resistant clones derived from DLD1 and those from HCT116, but the same among the clones if the parental cells were same. SMAD7 and IRF9 were candidate molecular markers to predict multidrug resistance.</jats:p>
<jats:p>Citation Format: Tomoki Yamano, Shuji Kubo, Aya Yano, Naohiro Tomita. Different mechanism of Oxaliplatin resistance in human colorectal cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5453. doi:10.1158/1538-7445.AM2015-5453</jats:p>