Characterization of mucin 2 expression in colorectal cancer with and without chemotherapies, in vivo and in vitro study

Abstract

Background: Colorectal cancer (CRC) is the third and second most prevalent cancer affecting males and females, respectively. 5-fluorouracil (5-FU) and irinotecan are the main chemotherapies for CRC. Down regulation of mucin 2 (MUC2) expression is associated with poor prognosis. Aim: This study examines the expression levels of MUC2 in response to treatment with 5-FU and/or irinotecan in vivo and in vitro. Method: HT29 CRC cells were treated with 5- FU and/or irinotecan, and the expression of MUC2 at mRNA and protein levels was examined by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC), respectively. CRC was induced in rats by injecting azoxymethane (AOM) prior to 5-FU treatment. Results: HT29 cells treated with 5-FU and/or irinotecan displayed a significant increase in the expression of MUC2. MUC2 mRNA expression was similar in response to monotherapy with irinotecan or 5 FU, and combinatorial treatment with irinotecan and 5-FU significantly increased MUC2 mRNA expression. Treatment of colon malignancy in rats with 5-FU resulted in increased expression of MUC2 compared with that in the positive control (rats treated with AOM only). The levels of MUC2 protein were restored and were similar to those in untreated rats. Conclusion: To our knowledge, this is the first in vitro study to report the effects of irinotecan treatment on MUC2 expression in CRC. MUC2 expression was increased by 5-FU and irinotecan. Therefore, further study could be undertaken to explore the potential use as a predictive marker in CRC.