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Effects of Jianpi Jiedu Recipe (健脾解毒方)on Reversion of P-Glycoprotein-Mediated Multidrug Resistance through COX-2 Pathway in Colorectal Cancer 被引量:17
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作者 隋华 朱惠蓉 +4 位作者 吴杰 NIKITIN Alexander Yu 蔡健锋 范忠泽 李琦 《Chinese Journal of Integrative Medicine》 SCIE CAS 2014年第8期610-617,共8页
Objective: To evaluate the underlying mechanism of Jianpi Jiedu Recipe (健脾解毒方, JJR) in the reversion of multidrug resistance concerning colorectal cancer in vitro and in vivo. Methods: Mice were treated orall... Objective: To evaluate the underlying mechanism of Jianpi Jiedu Recipe (健脾解毒方, JJR) in the reversion of multidrug resistance concerning colorectal cancer in vitro and in vivo. Methods: Mice were treated orally with JJR at a daily 4.25 g/(kg.day) or injected with vinblastine (VCR) 2.5 mg/(kg day) for 3 weeks after having been inoculated with HCT8N cells; tumor tissues were assayed by hematoxylin and eosin staining. Firstly, the effects of JJR on the expression of cyclooxygenase-2 (COX-2) were tested by real-time polymerase chain reaction (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 HCT8N and its COX-2 siRNA cells; the concentration of J JR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8N cells was evaluated by the MTT assay. Thirdly, real-time quantitative PCR and Western blot analysis were used to detect the multidrug resistance gene 1 (MDR1) mRNA and P-gp expression. Results: JJR had an inhibitory effect on the growth of tumors in vivo, and it, in combination with chemotherapeutic drugs, could reverse the drug-resistance of HCT8N cells and increase the sensitivity of HCT8N cells to VCR, DDP, 5-Fu, and THP. ICP-MS results showed that JJR could increase the concentration of drugs in HCT8/V cells (P〈0.01). Furthermore, it was shown that JJR could reverse drug resistance of colorectal cancer cells by decreasing MDR1 expression and P-gp level via downregulation of COX-2, which has been represented as one of the major mechanisms that contributes to the MDR phenotype (P〈0.01). Conclusion: JJR reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2 in MDRl/P-gp-mediated MDR colorectal cancer after chemotherapy. 展开更多
关键词 colorectal cancer multidrug resistance P-GLYCOPROTEIN multidrug resistance gene CYCLOOXYGENASE-2 jianpi jiedu recipe Chinese medicine
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