Abstract 219: Inhibition of CD133 expression induce the chemoresistance to 5-fluorouracil in the colon cancer cell line

Abstract

Background: The cancer stem cell (CSC) theory which postulates a small subset of tumor cells have the capacity in tumor initiation, progression and importantly resistance to chemotherapy. CD133 is a transmembrane glycoprotein that serves as a putative cancer stem cell (CSC) marker in colon cancer and its relationship with the chemoresistance has been on debate. In our previous clinical study, we found the patients with CD133+ colon cancer have better prognosis after 5 fluorouracil (5-FU) chemotherapy compared to CD133- tumors. Purpose: To understand the role of CSC marker expression in relation to chemoresistance in colon cancer, we evaluated the effect of CD133 inhibition in colorectal cancer (CRC) cell line on the genes expression which are related to chemoresistance or cell survival. Materials & Methods: CD133 siRNA transfection was performed on CD133+ colon cancer cell line (Caco-2). The proliferation assay used to detect the cytotoxic effect of 5-FU chemotherapy. The change in expression of chemoresistance related genes (AKT1, ABCG2 and MDR1) and cell survival related genes (survivin and beta-catenin) were evaluated by qRT-PCR and western blotting at 48hrs and 72hrs after CD133 siRNA transfection. Results: The proliferation assay demonstrated the increased chemoresistance of colon cancer cells after inhibition of CD133 expression when 5µM 5-FU was treated (p=0.0014). The mRNA expression of chemoresistance related genes (AKT1, ABCG2, MDR1) and cell survival related genes (survivin and β-catenin) were all significantly increased after transfection (p<0.05) but there was no significant changes in expression at the protein level of all genes. Conclusions: The inhibition of CD133 expression in CD133+colon cancer cell line induce the chemoresistance to 5-FU chemotherapy through the increased expression of chemoresistance related genes. Therefore, CD133 expression seems to be related with the chemosensitivity to 5-FU in colon cancer despite the mechanism needs to be proven. Citation Format: Mi-Ra Lee, Sun-Young Ji, Khalilullah Mia-Jan, Mee-Yon Cho. Inhibition of CD133 expression induce the chemoresistance to 5-fluorouracil in the colon cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 219. doi:10.1158/1538-7445.AM2014-219