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Synergistic cytotoxic effects of recombinant human tumor necrosis factor and Etoposide (VP16) or Doxorubicin on A2774 human epithelial ovarian cancer cell line
  1. G. Billi,*,
  2. M. Venturini,
  3. D. Piccini,
  4. S. Parodi*,
  5. R. Rosso,
  6. P. F. Conte and
  7. P. Russo*
  1. * Departments of Chemical Carcinogenesis and
  2. Medical Oncology, Istituto Nazionale per la Ricerca sul Cancro, V.le Bedetto XV, 10 I-16132 Genova, and
  3. Department of Medical Oncology, Ospedale Santa Chiara, Via Roma 67 I-56100 Pisa, Italy
  1. Address for correspondence: Patrizia Russo, Department of Chemical Carcinogenesis-Istituto Nazionale per la Ricerca sul Cancro, V.le Benedetto XV, 10 I-16132 Genova, Italy.


Recombinant human tumor necrosis factor (rHuTNF) is a cytokine, with some antitumor activity, released by stimulated monocytes-macrophages. In vivo and in vitro cytotoxicity studies testing the effectiveness of rHuTNF alone or in combination with chemotherapeutic agents have been carried out. We have evaluated the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell line in vitro (A2774), alone or in combination with Etoposide (VP16) or Doxorubicin (Doxo), some topoisomerase II (Topo II) targeted drugs, or in combination with Cisplatin (CDDP), a not Topo II interactive drug. Our results suggest that rHuTNF is directly cytotoxic and that it is also able to induce a potentiation of VP16- or Doxo-cytotoxicity, but it is unable to potentiate CDDP-cytotoxicity. These data represent a reasonable basis for combining rHuTNF with Topo II inhibitors within phase I studies. The combination regimen could be tested in ovarian cancer patients.

  • chemotherapy
  • cytotoxicity
  • Doxorubicin
  • ovarian cancer
  • rHuTNF
  • VP16.

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