Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma

作者：Wang, Chang-Fa^*; Wang, Ya-Qin; Huang, Fei-Zhou; Nie, Wan-Pin; Liu, Xun-Yang; Jiang, Xian-Zhen

来源：Journal of International Medical Research, 2013, 41(4): 964-974.

DOI：10.1177/0300060513483401

• Methyl jasmonate
• hepatocellular carcinoma
• multidrug resistance
• permeability (P)-glycoprotein
• ATPase activity
• H22 cell line
• H22/FAP cell line

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 invitro 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 (10mg/kg and 5mg/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.
Conclusion: 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.

• 出版日期2013-8
• 单位中南大学