Association between reversal of multidrug resistance by methyl jasmonate and P-glycoprotein ATPase activity in hepatocellular carcinoma
Chang-Fa Wang1, Ya-Qin Wang, Fei-Zhou Huang
1Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China. wangchangfa1978@hotmail.com
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.
Insights
Methyl jasmonate enhances chemotherapy effectiveness against multidrug-resistant hepatocellular carcinoma. This study shows methyl jasmonate combined with the FAP regimen significantly increases survival time in mice, offering a new strategy for cancer treatment.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Hepatocellular carcinoma (HCC) frequently develops multidrug resistance (MDR).
- Multidrug resistance limits the efficacy of standard chemotherapy regimens.
- Identifying novel agents to overcome MDR in HCC is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the potential of methyl jasmonate to reverse multidrug resistance in hepatocellular carcinoma.
- To evaluate the synergistic effects of methyl jasmonate with a standard chemotherapy regimen (FAP) in a mouse model of HCC.
Main Methods:
- Multidrug resistant H22 (H22/FAP) cells were established in vitro.
- Cytotoxicity was assessed using the MTT assay.
- In vivo efficacy was determined in BALB/c mice, measuring survival time and P-gp ATPase activity.
Main Results:
- Methyl jasmonate significantly potentiated the cytotoxicity of the FAP regimen against H22/FAP cells.
- Combination therapy with methyl jasmonate and FAP markedly increased mouse survival rates.
- Methyl jasmonate was observed to increase P-glycoprotein (P-gp) ATPase activity.
Conclusions:
- Methyl jasmonate demonstrates potential as an adjuvant therapy to overcome MDR in hepatocellular carcinoma.
- The combination of methyl jasmonate with the FAP regimen represents a promising novel strategy for HCC treatment.
- Further research into methyl jasmonate's mechanism in reversing MDR is warranted.
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