Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines

G. Giaccone, C. Kadoyama, R. Maneckjee, D. Venzon, R. B. Alexander, A. F. Gazdar

Research output: Contribution to journalArticle

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Abstract

Tumor necrosis factor α (TNF) exhibits cytotoxic activity on some solid tumors and has been reported to be synergistic with topoisomerase-II-targeted antineoplastic agents. A wide range of TNF concentrations (from 0 to 10,000 U/ml) was tested in 9 human lung cancer cell lines (5 small-cell and 4 non-small-cell carcinomas) using a semi-automated MTT assay. TNF was not cytotoxic in 8 cell lines, while an adenocarcinoma cell line was marginally sensitive to the cytokine. Using 125I-TNF we were able to show the presence of specific binding sites for TNF in 4/9 human lung cancer cell lines. Scatchard analysis of the marginally sensitive cell line showed high-affinity, saturable binding. With 5 cell lines we also tested whether TNF affected the cytotoxicity of doxorubicin and etoposide, 2 topoisomerase II-targeted drugs which are widely used in the therapy of lung cancer. No significant increase in cytotoxicity was seen when TNF was added to the 2 anti-neoplastic agents. In contrast to certain other human and mouse lines, human lung cancer cell lines appear to be resistant to TNF, despite the presence of the receptor in some of them; moreover, no synergistic effect of TNF and 2 topoisomerase-II-targeted drugs was evident in these human cell lines.

Original languageEnglish (US)
Pages (from-to)326-329
Number of pages4
JournalInternational Journal of Cancer
Volume46
Issue number2
DOIs
StatePublished - 1990

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Type II DNA Topoisomerase
Lung Neoplasms
Tumor Necrosis Factor-alpha
Cell Line
Pharmaceutical Preparations
Etoposide
Antineoplastic Agents
Doxorubicin
Adenocarcinoma
Binding Sites
Cytokines
Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines. / Giaccone, G.; Kadoyama, C.; Maneckjee, R.; Venzon, D.; Alexander, R. B.; Gazdar, A. F.

In: International Journal of Cancer, Vol. 46, No. 2, 1990, p. 326-329.

Research output: Contribution to journalArticle

Giaccone, G. ; Kadoyama, C. ; Maneckjee, R. ; Venzon, D. ; Alexander, R. B. ; Gazdar, A. F. / Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines. In: International Journal of Cancer. 1990 ; Vol. 46, No. 2. pp. 326-329.
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