TNF receptor number-dependent cytotoxicity to TNF-resistant human esophageal cancer cell lines by combination with recombinant human necrosis factor and hyperthermia.
The synergistic effect of recombinant human tumor necrosis factor (rh-TNF) and hyperthermia on five established cell lines of human esophageal cancer (SGF series) was analyzed by in vitro assays. The SGF cell lines were either resistant or slightly sensitive to rh-TNF. However, they became highly sensitive to rh-TNF even at as low a concentration as 10 U/ml and dose-dependently when combined with hyperthermia (43.5 degrees C, 60 min). This result was due to synergistic effects of rh-TNF and hyperthermia, and the degree of the effect increased with the hyperthermic temperature and TNF concentration. The number of TNF receptors per cell varied widely from cell line to cell line, from 4,400 to 23,100, which did not correlate to the extent of cytotoxicity by rh-TNF alone. The degree of synergistic effect of rh-TNF and hyperthermia was evaluated quantitatively in terms of a Synergistic Index (S. I. = Predicted cell viability/Experimental cell viability): A significant correlation was found between the logarithmic S. I. and the number of TNF receptors. These findings indicated that the combination of rh-TNF and hyperthermia produced a significant antitumor effect even on the cell lines poorly sensitive to TNF in a receptor-dependent manner, although the cellular sensitivity to TNF alone was not directly correlated to the number of TNF receptors.
Saito
T
T
Second Department of Surgery, Toyama Medical and Pharmaceutical University.
Kato
H
H
Saito
M
M
Karaki
Y
Y
Tazawa
K
K
Fujimaki
M
M
D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007036:Hypothermia, Induced; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha