Abstract 779: Osteopontin gene expression is associated with 5-fluorouracil drug resistance in colon cancer

Abstract

Abstract Background: Resistance to chemotherapeutic drugs complicates the treatment of cancer patients. The extracellular matrix protein osteopontin (OPN) plays multiple roles in the proliferation and metastasis of cancer cells. We therefore attempted to determine whether OPN expression correlated with drug resistance. Methods: OPN expression in the HCT 116 colon cancer cell line was inhibited by an OPN-short interfering RNA (siRNA). We determined the cytotoxic effect (IC50) of 5-fluorouracil (5FU) on these cells. Patients with recurrence or colorectal cancer or harbored residual tumor cells were treated with S-1-based chemotherapy. The levels of OPN mRNA expression in the tumors were determined and compared with the patients’ responses to chemotherapy. Results: The IC50 of 5FU for HCT 116 cells transfected with the OPN-siRNA was 32.9 μM. In contrast, the IC50 values for cells transfected with a negative control siRNA, mock-transfected cells, or untreated cells were 6.58 μM, 7.08 μM, and 6.76 μM, respectively (P<0.001). The level of OPN mRNA expression in the S-1 non-responder group was significantly lower than that of the responder group (P = 0.0387). Survival analysis revealed no significant difference between the responder and non-responder groups (P = 0.8737). Conclusions: The level of OPN expression plays a role in the resistance of colorectal tumor cells to 5FU. Citation Format: Go Nakajima, Hidekazu Kuramochi, Masakazu Yamamoto, Kazuhiko Hayashi. Osteopontin gene expression is associated with 5-fluorouracil drug resistance in colon cancer. [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 779. doi:10.1158/1538-7445.AM2014-779