Cantharidin reverses multidrug resistance of human hepatoma HepG2/ADM cells via down-regulation of P-glycoprotein expression

Cancer Lett. 2008 Dec 8;272(1):102-9. doi: 10.1016/j.canlet.2008.06.029. Epub 2008 Aug 13.

Abstract

Multidrug resistance (MDR) is a serious obstacle encountered in cancer treatment. In this study, we established an in vitro multiple drug resistant HepG2 cell line (HepG2/ADM), and characterized its MDR. This model was used to screen potential candidate chemosensitisers from over 200 purified naturally occurring compounds extracted from plants and animals. Cantharidin was found to have a significant reversal on MDR in our model. Further, our results showed that Cantharidin could significantly inhibit P-gp (P-glycoprotein) expression, mRNA transcription, as well as MDR1 promoter activity. These results suggest that Cantharidin is a novel and potent MDR reversal agent and may be a potential adjunctive agent for tumor chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Cantharidin / pharmacology*
  • Cantharidin / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Down-Regulation
  • Drug Resistance, Multiple / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Humans
  • Kidney
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Enzyme Inhibitors
  • RNA, Messenger
  • RNA, Neoplasm
  • Cantharidin