Experimental Studies On The Induction Of Thymidine Phosphorylase And The Sensitivity To The Prodrug Of 5-Fluorouracil In Vitro

Objectives:5-Fluorouracil has been used in the treatment of a variety of tumor types, unfortunately its response rate was only around 15%,and serious sides were also observed . Capecitabine(Xeloda ?) is a novel pr-drug of 5-FU that rapidly absorbed from the gastrointestinal tract after oral administration. Capecitabine is preferentially converted to the cytotoxic 5-FU in target tumor tissue through a series of 3 metabolic steps, in which thymidine phsophorylase (TP) is a rate-limiting enzyme. TP shows higher concentrations in tumor tissue than normal tissue in numerous tumors, and resulted in higher 5-FU concertrations selectively in tumor tissue. Here,we focus on TP, inducing TP to increase sensitivity to fluoropyridine drugs. Methods:Four colorectal and breast cancer cell lines were cultured in vitro.It was done to assay the cytoxicity with MTT staining. Cancer cells were cultured and then treated with fresh RPMI-1640 with 10%FCS containing the various concentration TNF-α or Dotoxal. The TP level of tumor cell was mearsured by E LISA. And then the assay was done with MTT staining for the cells treated with small concentration TNF-α or Dotoxal.Result:1. The TP in Lovo or SW620 was not displayed, and it was significantly higher in MCF-7 than in MCF/ADR.2. TNF-α and Dotoxal caused a concentration-and time-dependent increase in the levels for TP.3. The TP level of MCF-7 has displayed a 1.27 fold increase, while IC50 of it has displayed a 1.33 fold decrease. However ,the sensitivity to 5-FU did not increase . Conclusions:1. The TP levels in tumor cells are very different...