Relationship between Expression of Thy- midylate Synthase mRNA and Resistance of Colon and Gastric Cancer Cells to 5-FU

ABSTRACT

PURPOSE: Thymidylate synthase (TS) is an important target for chemotherapeutic drugs such as 5-fluorouracil (5-FU). Overexpression of TS has been linked to chemotherapy resistance, but their relationship was not completely understood. We compared the expression level of TS with resistance of colon and gastric cancer cell lines to 5-FU. METHODS: Expression of TS mRNA was determined by RT-PCR assay in 9 colon and 10 gastric cancer cell lines. Cytotoxicity of 5-FU was determined by MTT assay. Apoptosis was determined using propidium iodide staining by flow cytometry. RESULTS: All cancer cell lines tested showed differential levels of TS mRNA expression. Colon cancer cell Colo320 (the highest expression of TS) was more resistant to 5-FU than SNU-C1 (the lowest expression of TS) was. Flow cytometry also showed that 5-FU induced apoptosis less in Colo320 than SNU-C1. But in gastric cancer cells SNU-1 (the highest expression of TS) was not resistant to 5-FU than SNU-16 (the lowest expression of TS) was. CONCLUSIONS: The high level of expression of TS was correlated with resistance of colon cancer cells to 5-FU, but not in gastric cancer cells. Thus, TS may be differently involved in the resistance of gastric and colon cancer cells to 5-FU, which may depend on the origin of cancer cells and status of apoptosis related genes.