title: Effects of Jianpi Jiedu Recipe on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer.
abstract: OBJECTIVE
  To evaluate the underlying mechanism of Jianpi Jiedu Recipe (, 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 HCT8/V 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 (ICPMS) in HCT8/V and its COX-2 siRNA cells; the concentration of JJR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8/V 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 HCT8/V cells and increase the sensitivity of HCT8/V 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).
  
  
  CONCLUSIONS
  JJR reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2 in MDR1/P-gp-mediated MDR colorectal cancer after chemotherapy.
authors.affiliation: Department of Medical Oncology, Shuguang Hospital & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.forename: Hui-rong
authors.initials: HR
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Nikitin
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Cai
authors.forename: Zhong-ze
authors.initials: ZZ
authors.lastname: Fan
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009944:Organoplatinum Compounds / Q000378:metabolism; D000077150:Oxaliplatin; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004365:Drugs, Chinese Herbal; D009944:Organoplatinum Compounds; D034741:RNA, Small Interfering; C000596357:jianpi jiedu; D000077150:Oxaliplatin; D049452:Green Fluorescent Proteins; D014747:Vinblastine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
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