Cytotoxicity of combinations of IFN-beta and chemotherapeutic drugs

J Interferon Cytokine Res. 2002 Aug;22(8):873-80. doi: 10.1089/107999002760274881.

Abstract

Interferon-beta (IFN-beta) induces various antiproliferative activities. In solid tumor cells, IFN-beta inhibits cell cycle progression, which mainly occurs as S phase accumulation. The IFN-beta-induced cell cycle effect has been implicated in the antitumor effect of combinations of IFN-beta and chemotherapeutic drugs. In this report, we characterized the viability of various human tumor cells in vitro after combination treatment with IFN-beta protein and the chemotherapeutic drugs, cis-platinum (II) diamine dichloride (cisplatin), 5-fluorouracil (5-FU), paclitaxel (Taxol) and gemcitabine. IFN-beta could significantly potentiate the cytotoxicity of these chemotherapeutic drugs. The potentiating effect was observed after pretreatment of tumor cells with IFN-beta but did not require the constant presence of IFN-beta. The potentiating effect correlated with the sensitivity of the tumor cells to the IFN-beta-induced cytotoxicity. Furthermore, chemotherapeutic drugs also potentiated the cytotoxicity of IFN-beta. We conclude that the cell cycle effect per se did not determine the ability of IFN-beta to potentiate the cytotoxicity of chemotherapeutic drugs. We suggest that the combination of local IFN-beta gene therapy with chemotherapy could be an effective cancer treatment.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Breast Neoplasms / pathology
  • Carcinoma / pathology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Division / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Drug Synergism
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology
  • Gemcitabine
  • Humans
  • Interferon-beta / administration & dosage
  • Interferon-beta / pharmacology*
  • Lung Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Uterine Cervical Neoplasms / pathology

Substances

  • Deoxycytidine
  • Interferon-beta
  • Paclitaxel
  • Cisplatin
  • Fluorouracil
  • Gemcitabine