Rifampicin enhances anti-cancer drug accumulation and activity in multidrug-resistant cells

Biochem Pharmacol. 1995 May 11;49(9):1255-60. doi: 10.1016/0006-2952(95)00045-2.


Rifampicin, a semi-synthetic antibiotic used in the treatment of tuberculosis and belonging to the chemical class of rifamycins, was examined for its effect on anti-cancer drug accumulation and activity in multidrug resistant cells overexpressing P-glycoprotein (P-gp). Rifampicin was shown to strongly enhance vinblastine accumulation in both rat hepatoma RHC1 and human leukemia K562 R7 multidrug resistant cells, but had no effect in rat SDVI drug-sensitive liver cells. By contrast, two other rifamycins, rifamycins B and SV, had no or only minor effect on vinblastine accumulation in RHC1 cells. Efflux experiments revealed that rifampicin was able, like the well-known chemosensitizer agent verapamil, to decrease export of vinblastine out of resistant cells. Rifampicin, when used at a concentration close to plasma concentrations achievable in humans (25 microM), was able to increase sensitivity of RHC1 cells to both vinblastine and doxorubicin. Rifampicin was also demonstrated to inhibit P-gp radiolabeling by the photoactivable P-gp ligand azidopine, thereby suggesting that the antituberculosis compound can interfere directly with P-gp drug binding sites. These results thus indicate that rifampicin was able to down-modulate P-gp-associated resistance through inhibition of P-gp function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / analysis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Cell Division / drug effects
  • Cell Line
  • Doxorubicin / metabolism
  • Drug Resistance, Multiple
  • Drug Synergism
  • Humans
  • Rats
  • Rifampin / pharmacology*
  • Structure-Activity Relationship
  • Vinblastine / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Vinblastine
  • Doxorubicin
  • Rifampin