Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines.
Tumor necrosis factor alpha (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 10 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.
Giaccone
G
G
NCI-Navy Medical Oncology Branch, Bethesda MD 20814.
Kadoyama
C
C
Maneckjee
R
R
Venzon
D
D
Alexander
R B
RB
Gazdar
A F
AF
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002460:Cell Line; D004250:DNA Topoisomerases, Type II; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000032:analysis / Q000188:drug therapy*; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D004337:Drug Carriers; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D004317:Doxorubicin; D004250:DNA Topoisomerases, Type II