Cytotoxicity of combinations of IFN-beta and chemotherapeutic drugs.
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.
Brickelmaier
Margot
M
Biogen, Inc., Cambridge, MA 02142, USA.
Carmillo
Amie
A
Goelz
Susan
S
Barsoum
James
J
Qin
Xiao-Qiang
XQ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D000093542:Gemcitabine
D003841:Deoxycytidine; D016899:Interferon-beta; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine