Klostergaard J, Akimaru Y, Tomasovic S P
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Int J Hyperthermia. 1996 Jan-Feb;12(1):97-114. doi: 10.3109/02656739609023693.
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.
与在37℃持续处理相比，肿瘤坏死因子（TNF）敏感的小鼠L929细胞在43℃致敏温度（ST）下进行30分钟的降温加热（SDH），随后在40.5℃测试温度（TT）下孵育24小时后，对TNF的反应增强了约1000倍。小鼠EMT-6乳腺腺癌细胞的TNF抗性表型可通过在40.5℃的TT下加热24小时来克服，并且通过在ST下预热长达60分钟可进一步提高其对TNF的敏感性。TNF敏感的HCT-15人结肠腺癌细胞的反应与L929细胞有些相似，只是仅在40.5℃加热就使TNF敏感性增加了约2.5个对数。TNF抗性的DLD-1人结肠腺癌细胞的反应与EMT-6细胞相似。相比之下，三种正常细胞系对所检测的任何TNF/SDH处理均表现出更大的抗性。我们的结果表明，SDH可能克服肿瘤细胞对TNF的抗性或增强其反应，同时将对正常细胞的细胞毒性作用降至最低。
