Reversing resistance of multidrug-resistant hepatic carcinoma cells with parthenolide

Future Oncol. 2013 Apr;9(4):595-604. doi: 10.2217/fon.13.15.

Abstract

Aim: To investigate the mechanism of reversing resistance of a hepatic carcinoma multidrug-resistant cell BEL-7402/5-FU with parthenolide (PTL).

Materials & methods: BEL-7402/5-FU cells were treated with different concentrations of PTL and/or 5-fluorouracil. The proliferation inhibition rates, NF-κB, P-glycoprotein, MRP, Bcl-2, WNT1 and p53 levels were determined.

Results: The results showed that PTL did not only have proliferation inhibition influence on BEL-7402/5-FU in a concentration-dependent manner, but also significantly increased the proliferation inhibition role of 5-fluorouracil on BEL-7402/5-FU, to reverse the resistance of hepatic carcinoma-resistant cells. PTL could also inhibit the NF-κB activity and the expression of P-glycoprotein, MRP, Bcl-2 and WNT1, and increase the expression of p53.

Conclusion: Our research suggests that clinical administration of PTL may be useful for hepatic carcinoma patients.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects*
  • Fluorouracil / pharmacology
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • NF-kappa B / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sesquiterpenes / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism
  • Wnt1 Protein / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antimetabolites, Antineoplastic
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • Tumor Suppressor Protein p53
  • Wnt1 Protein
  • parthenolide
  • Fluorouracil