title: Effect of interferon gamma and tumour necrosis factor alpha on sensitivity to cisplatin in ovarian carcinoma cell lines.
abstract: This study aimed to investigate whether the biological response modifiers (BRM) interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN gamma was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Clark
authors.forename: M A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: T
authors.initials: T
authors.lastname: Hurst
authors.forename: B G
authors.initials: BG
authors.lastname: Ward
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000628:therapy; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002945:Cisplatin