Step-down heating enhances the cytotoxicity of human tumour necrosis factor on murine and human tumour cell lines in vitro

Abstract

The response of tumour necrosis factor (TNF)-sensitive murine L929 cells to TNF was enhanced ∼ 1000-fold after stepdown heating (SDH) for 30 min at a sensitizing temperature (ST) of 43d`C and a subsequent 24 h incubation at a test temperature (TT) of 40.5d`C, compared to continuous treatment at 37d`C. The TNF-resistant phenotype of murine EMT-6 mammary adenocarcinoma cells could be overcome by 24 h heating at a TT of 40.5d`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 a ∼ 2.5 log increase in TNF-sensitivity due solely to heating at 40.5d`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.

Key Words:

• Stepdown heating
• TNF
• tumour cells