Silibinin對CT-26小鼠結腸腫瘤抗藥性醣蛋白P-glycoprotein之調節作用

Abstract

Multidrug resistance (MDR) is closely associated with the failure of cancer chemotherapy. P-glycoprotein (P-gp) is the protein product encoded by mdr1 gene. The function of P-gp is to efflux chemotherapeutic drugs, thereby reducing the intracellular drug concentrations. Recent studies have shown that natural phytochemicals exhibited anti-cancer and P-gp modulatory effects. For example, the anti-cancer activity of silibinin, a flavonoid compound, has been reported in several in vitro and in vivo models. The objective of the present study was to investigate the effect of silibinin on P-gp activity using the murine CT-26 colon carcinoma line and its animal tumor model. The cytotoxic effect of silibinin on CT-26 cells (CT-26NVT) and CT-26/MDR in vitro was evaluated by an MU assay. Treatment of cells with non-toxic concentrations (＜50 μM) of silibinin for 1 hr markedly inhibited the P-gp activity in CT-261WT and CCT-26/MDR cells, as measured by calcein accumulation. The effect of silibinin on the P-gp activity of CT-26/MDR tumor implants was also investigated. BALB/c mice bearing tumor implants were daily treated with silibinin (200 mg/kg) by gavage, and received ip injections of doxorubicin (DOX; 10 mg/kg/week for 3 weeks) when the tumor implants reached the size of 70-250 mm^3. The results showed that daily treatment of mice with silibinin did not affect the growth of tumor implants, as compared to the control group. In addition, silibinin treatment did not augment the anti-cancer effect of DCX. Taken together, our data demonstrated that the in vivo growth of CT-26/MDR tumor implants was unaffected by silibinin treatment, although the P-gp activity of the cells in vitro was suppressed by silibinin.