Step-down heating enhances the cytotoxicity of human tumour necrosis factor on murine and human tumour cell lines in vitro.
The response of tumour necrosis factor (TNF)-sensitive murine L929 cells to TNF was enhanced approximately 1000-fold after step-down heating (SDH) for 30 min at a sensitizing temperature (ST) of 43 degrees C and a subsequent 24 h incubation at a test temperature (TT) of 40.5 degrees C, compared to continuous treatment at 37 degrees C. The TNF-resistant phenotype of murine EMT-6 mammary adenocarcinoma cells could be overcome by 24 h heating at a TT of 40.5 degrees C, and their sensitivity to TNF could be further increased by preheating at the ST for up to 60 min. The response of TNF-sensitive HCT-15 human colon adenocarcinoma cells was somewhat similar to that of L929 cells except that there was u approximately 2.5 log increase in TNF-sensitivity due solely to heating at 40.5 degrees C. The response of TNF-resistant DLD-1 human colon adenocarcinoma cells was similar to that of EMT-6 cells. In contrast, three normal cell lines demonstrated greater resistance to any TNF/SDH treatment examined. Our results suggest that SDH may overcome the resistance or enhance the response of tumour cells to TNF while minimizing cytotoxic effects on normal cells.
Klostergaard
J
J
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Akimaru
Y
Y
Tomasovic
S P
SP
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004351:Drug Resistance; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D010641:Phenotype; D013696:Temperature; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D006360:Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha