[Enhanced cytotoxicity of antineoplastics by interferon].
Cytotoxicities of bleomycin (BLM), vincristine (VCR) and adriamycin (ADM), and influence of interferon (IFN) on their effects were examined on three tumor cell lines of HeLa, HSG (established from human submandibular gland) and Muko cells (derived from mucoepidermoid tumor of the upper jaw). Both human natural interferon beta (IFN beta) and recombinant interferon gamma (IFN gamma) exhibited anticellular activities. Antiproliferative action, and DNA and protein synthesis inhibition of each anticancer drug on tumor cells were enhanced by a few hrs' IFN (100 IU/ml) pretreatment. In these, DNA synthesis inhibition was more exaggerated. Cooperative IFN effects were additive in general while showing slight synergistic inhibitory action on DNA synthesis. Enhanced in vitro cytotoxic effects of the anticancer drugs by IFNs were similarly identified in tumor cell-inoculated nu/nu mice which were treated twice a week with locally injected IFN gamma and antineoplastics. Proliferation of inoculated tumor cells was significantly suppressed by IFN gamma, and a cooperative effect of the IFN and drugs was obtained. Concentrations of intracellular anticancer drugs were heightened by IFN pretreatment. From these results, IFN seemed to contribute to the enhanced anticellular effects of BLM, VCR and ADM by affecting cellular uptake of the drugs.
Yoneda
K
K
Department of Dentistry and Oral Surgery, Kochi Medical School.
Yamamoto
T
T
Osaki
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma