Choriocarcinoma Resistant Cell Line 5-FU / FUDR Metabolic Pathways Related Research

Objective:Choriocarcinoma is a highly malignant tumor, which is relatively common in child-bearing ages of females. Chemotherapy is so far the main treatment. Drug resistance to choriocarcinoma is the primary cause which leads to treatment failure. It can be congenital or acquired after chemotherapy. Most of the drug resistance in choriocarcinoma is acquired, including pharmacological and cytological mechanisms. This study is based on the clearly understood intracellular5-FU/FUDR metabolic pathway, to identify the connection between the gene expression of related enzymes in the pathway and the drug resistance of choriocarcinoma cells.Method:The chemosensitivity, growth curve, cell cycle, population doubling time and P-gp expression were determined through different assays. The gene expression of the enzymes involved in the intracellular5-FU/FUDR metabolic pathway of both parent cells and drug resistant cells were measured using real-time qPCR. SELDI TOF MS was used to identify whether there are different protein peaks between different cell strains.Result:Comparing with parent cells, there were morphological changes, elevated p-gp expression, enhanced drug resistance in drug resistant cells, no significant differences in cell cycle, cell growth velocity and doubling time. The DPD and TP gene expression were decreased and the TK and TS gene expression were increased in drug-resistant cells comparing with parent cells. The result of SELDI showed5-FU B concentration(0.25mg/ml) drug resistant cells showes three different protein peaks.Conclusion:DPD, TP, TK and TS are key enzymes in the intracellular5-FU/FUDR metabolic pathway. The gene expression of those enzymes were significant different between parent cells and drug resistant cells.