title: Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma.
abstract: OBJECTIVE
  To study the effects of methyl jasmonate on multidrug resistance in a mouse model of hepatocellular carcinoma.
  
  
  METHODS
  Multidrug resistant H22 (H22/FAP) hepatocellular carcinoma cells were produced in vitro by continuous exposure to increasing doses of doxorubicin, cisplatin and 5-fluorouracil (FAP regimen). Cell toxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide (MTT) assay. Survival time was calculated for BALB/c mice that received intraperitoneal injections of H22/FAP cells followed by treatment with methyl jasmonate or verapamil in combination with FAP for 7 days. Adenosine triphosphate (ATP) hydrolysis was used to measure the activity of permeability-glycoprotein (P-gp) ATPase activity in plasma membranes.
  
  
  RESULTS
  The MTT assay showed that methyl jasmonate significantly enhanced the cytotoxicity of the FAP regimen in multidrug resistant H22/FAP cells. Methyl jasmonate (10 mg/kg and 5 mg/kg) combined with FAP significantly increased survival time in BALB/c mice by 44.25% and 48.01%, respectively, compared with FAP. Methyl jasmonate increased P-gp ATPase activity.
  
  
  CONCLUSIONS
  The combined use of methyl jasmonate and the FAP regimen might be a novel strategy for overcoming the multidrug resistance often observed in hepatocellular carcinoma.
authors.affiliation: Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China. wangchangfa1978@hotmail.com
authors.forename: Chang-Fa
authors.initials: CF
authors.lastname: Wang
authors.forename: Ya-Qin
authors.initials: YQ
authors.lastname: Wang
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Huang
authors.forename: Wan-Pin
authors.initials: WP
authors.lastname: Nie
authors.forename: Xun-Yang
authors.initials: XY
authors.lastname: Liu
authors.forename: Xian-Zhen
authors.initials: XZ
authors.lastname: Jiang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000085:Acetates / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin; D003517:Cyclopentanes / Q000494:pharmacology*; D004317:Doxorubicin; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D054883:Oxylipins / Q000494:pharmacology*; D016019:Survival Analysis; D005641:Tegafur; D014498:Uracil; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000085:Acetates; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D054883:Oxylipins; D005641:Tegafur; D014498:Uracil; D004317:Doxorubicin; D000255:Adenosine Triphosphate; C072239:methyl jasmonate; D014700:Verapamil; D002945:Cisplatin
keywords: ATPase activity; H22 cell line; H22/FAP cell line; Methyl jasmonate; hepatocellular carcinoma; multidrug resistance; permeability (P)-glycoprotein