[Potentiation of the cytotoxic effects of anticancer drugs on human genitourinary neoplastic cells by recombinant gamma-interferon].
Experiments were performed to ascertain whether or not the cytotoxic effects of various anticancer drugs on five human genitourinary malignant cell lines would be enhanced by recombinant gamma-type interferon. The cells used were as follows: HeLa cells from a uterine cervix cancer, HT-1376 and EJ cells from bladder cancers, ACHN cells from a renal cancer, and PC-3 cells from a prostatic cancer. The effects of the drugs were studied by colony formation assay. The following drugs were used: two metabolic antagonists. cytosine arabinoside (Ara-C) and 5-fluorouracil (5-FU), three antibiotics: adriamycin (ADM), mitomycin C (MMC) and peplomycin (PEP), two alkylating agents: nimustine hydrochloride (ACNU) and melphalan, one vinca alkaloid: vincristine (VCR) and one other drug: cisplatin (CDDP). Interferon used was a preparation of recombinant gamma-type interferon. PEP showed synergistically enhanced cytotoxic effects on HeLa, EJ, HT-1376, and ACHN cells by concomitant application with gamma-IFN. Synergistic cytotoxicity was also detected against HeLa, EJ and ACHN by combined treatment with ADM and gamma-IFN. A similar enhanced cytotoxicity was demonstrated in HT-1376 and PC-3 by 5-FU treatment with gamma-IFN. MMC showed enhanced cytotoxicity only against ACHN cells in the presence of gamma-IFN. The cytotoxic effects of PEP on cells were increased by lower concentrations of gamma-IFN compared with those of other drugs. DNA, RNA and protein synthesis were examined in HeLa cells following combined exposure to PEP and gamma-IFN. The combined therapy was found to produce a specific decrease in DNA synthesis, while yielding no significant inhibition of intracellular RNA and protein synthesis.
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002460:Cell Line; D002478:Cells, Cultured; D002945:Cisplatin / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000627:therapeutic use; D014410:Tumor Stem Cell Assay; D014565:Urogenital Neoplasms / Q000473:pathology*; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D003561:Cytarabine; D015376:Nimustine; D014750:Vincristine; D004317:Doxorubicin; D007371:Interferon-gamma; D002945:Cisplatin