Objective:To investigate the multi-drug resistance reversal effects of Curcumin on xenografts derived from multidrug resistant human colon carcinoma cell line HCT-8/VCR and the possible mechanism.Methods:Nude mice bearing HCT-8/VCR tumors were randomized into four groups: group A:the control group, group B:VCR group, group C:Curcumin group, group D:Curcumin plus VCR group.Tumor specimens were collectted from the mice in each group two weeks after the interventions.Morphology of xenografts were investigated by HE staining.The expressions of MDRl,P-glycoprotein(P-gp) and Survivin were observed with reverse transcriptase PCR and Westernblot assay respectively.Results : Curcumin plus VCR significantly inhibited the growth of xenografts, the xenografts, weight of the co-administration group were lower than that of the other three groups(P﹤0.05 ). RT-PCR,Westernblot showed that expression of MDRl,P-glycoprotein(P-gp) and Survivin was significantly reduced in the Curcumin group and the Curcumin plus VCR group compared to the control group(P﹤0.05 ). HE biopsy revealed that Curcumin plus VCR group and Curcumin group had more lymphocytic infiltration, more nuclear pyknosis, fewer mitotic figures, necrosis is more extensive compared to the other groups.Conclusion:Curcumin has strong reversal effects on MDR in HCT-8/VCR cells through multiple routes including downregulating MDR1 and Survivin mRNA and protein expression.
|