The combined effect of interferon-beta and cytostatic drugs on human tumor cell lines in vitro.
Three human tumor cell lines (one osteosarcoma and two neuroblastoma lines) were assessed for combined interferon-beta (IFN-beta)/chemotherapeutic drug antigrowth effect under in vitro conditions. Two different methods to measure this effect were used: colony formation in soft agar and counting of cells growing as monolayers. The cells were incubated with a chemotherapeutic drug (adriamycin, dacarbazine, actinomycin D, cis-platinum, methotrexate, VP-16-213, or vincristine) at relevant concentrations for 1 h, washed twice, and incubated with IFN-beta in concentrations ranging from 100 to 1000 IU for continuous exposure. All combinations resulted in an additive or synergistic combination effect with one exception: methotrexate/IFN-beta in the monolayer method after 1 week, a combination which was additive after 3 weeks however. The combinations VP-16-213/IFN-beta and cis-platinum/IFN-beta produced the most pronounced synergistic effects. A statistical evaluation of the null hypothesis for additivity was done. These results provide a rationale for designing clinical studies combining IFN-beta with current chemotherapeutic drugs.
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D009447:Neuroblastoma / Q000188:drug therapy / Q000628:therapy; D012516:Osteosarcoma / Q000188:drug therapy / Q000628:therapy
D000970:Antineoplastic Agents; D007370:Interferon Type I