Abstract 2608: Regulation of response to oxaliplatin by wnt/β-catenin in colon cancer cell lines.

Abstract

Abstract Background: Oxaliplatin is the standard treatment chemotherapy agent in patients with metastatic colorectal cancer. However, most patients developed the progressive disease after treatment with oxaliplatin due to chemotherapy resistance. Unfortunately the mechanism of resistance of oxaliplatin is unclear. Wnt/β-catenin signaling pathway may play a role in oncogenesis in many cancer and also involve in the control the cancer progression and metastasis throughout the interaction with the tumor microenvironment. In this study, we investigated the response to oxaliplatin regulated by wnt/β-catenin pathway in colon cancer cell line. Method: We used SNU-C2A and HCT116 human colon cancer cell lines. After comparing β-catenin expression in SNU-C2A and HCT116 cells through western blot, we exposed these two cell lines to gradient concentrations of oxaliplatin for 48hrs to examine the sensitivity. The viability was determined by Neutral Red uptake assay (NR assay). To construct a gene silenced cell line, a siRNA against β-catenin was transfected in HCT116 cells. Besides, we stimulated SNU-C2A cells with human recombinant Wnt3a (rhWnt3a) protein to up regulate the β-catenin and estimated the change of sensitivity for oxaliplatin,respectively. We also constructed a HCT116-cis cell line which showed oxaliplatin-resistance. It has been made by long-term exposure to oxaliplatin. Result: β-catenin was highly expressed in HCT116 cell line relatively higher than in SNU-C2A cell line. Through the sensitivity test to oxalipatlin, we confirmed that SNU-C2A cells were more sensitive to oxaliplatin than HCT116 cells. When we transfected β-catenin siRNA into the HCT116 cell line, the cell viability was decreased about 20-50% after oxaliplatin treatment. After rhWnt3a treatment,we confirmed the expression of β-catenin and c-myc was up regulated in SNU-C2A cell line by western blot. After treatment with oxaliplatin, we found that the cell viability was reduced in SNU-C2A cells with β-catenin overexpressing. Moreover,HCT116-cis, oxaliplatin-resistance induced cell line, showed not only the increased protein level of β-catenin but also the upper viability for oxaliplatin compared with HCT116. Conclusion Based on our data, β-catenin is one of the crucial factors to determine the resistance for oxaliplatin in colon cancer cells. Currently we are conducting the analysis with human tissue, and exploring the possible mechanism of resistance developmend to oxaliplatin. Citation Format: Myung Ah Lee, Jin Hee Park. Regulation of response to oxaliplatin by wnt/β-catenin in colon cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2608. doi:10.1158/1538-7445.AM2013-2608