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.

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.

• Authors: Chang-Fa Wang, Ya-Qin Wang, Fei-Zhou Huang, Wan-Pin Nie, Xun-Yang Liu, Xian-Zhen Jiang
• Journal: The Journal of international medical research (J Int Med Res) Vol. 41 Issue 4 Pg. 964-74 (Aug 2013) ISSN: 1473-2300 [Electronic] England
• PMID: 23867448 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Acetates
• Antineoplastic Agents
• Cyclopentanes
• Oxylipins
• Tegafur
• Uracil
• Doxorubicin
• Adenosine Triphosphate
• methyl jasmonate
• Verapamil
• Cisplatin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, metabolism)
• Acetates (pharmacology)
• Adenosine Triphosphate (metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cisplatin
• Cyclopentanes (pharmacology)
• Doxorubicin
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• Injections, Intraperitoneal
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental
• Oxylipins (pharmacology)
• Survival Analysis
• Tegafur
• Uracil
• Verapamil (pharmacology)