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Effets of JianpiJieduRecipeonReversion of P-glycoprotein-mediated Multidrug Resistance through COX-2 Pathway in Colorectal Cancer

摘要To evaluate the underlying mechanism of JianpiJiedu Recipe(健脾解毒方, JJR) in the reversion of multidrug resistance concerningcolorectal cancerin vitro and in vivo.Methods:Micewere treatedorally with JJRat a daily 4.25g/(kg·day)orinjectedwithvinblastine(V CR) 2.5 mg/(kg·day)for 3 weeks after having been inoculated with HCT8/V cells; tumor tissues were assayed byhernatoxylin andeosin staining.Firstly, the effects of J JR on the expression of cyclooxygenase-2 (COX-2)were tested by real-time PCR technique and COX-2 gene silenced by siRNA.Secondly, the variation of intracellular concentration of oxaliplatin (L-OHP)was evaluated by the inductively coupled plasma mass spectroscopy (ICP-MS) in HCT8/V and its COX-2 siRNAcells, the concentration of J JR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8/V cells was evaluated by the MTT assay. Real-time quantitative PCR and Western blot analysis were used to detect the multidrug resistance gene I(MDR1) mRNA and P-gp expression.Results: JJRhad aninhibitory effect on the growth of tumors in vivo, and it,in cornbination with chemotherapeutic drugs, could reverse the drug-resistance of HCT8/V cells and increase the sensitivity of HCT8/V cells to VCR, DDP, 5-Fu, and THE ICP-MS results showed that JJR could increase the concentration of drugs in HCT8/V cells. Furthermore, it was shown that J JRcould reverse drug resistance of colorectal cancer cells by decreasing MDRI expression and P-gp Ievel via downregulation of COX-2, which has been represented as one of the major mechanisms that contributes to the MDR phenotype. Conclusion: JJRreversedmultidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2inMDR l/P-gp-mediated MDR colorectal cancer after chemotherapy

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