Soejima S, Hidaka K, Kuwano M, Hisatsugu T
Department of Surgery, Saga Medical School, Japan.
Cancer Lett. 1991 Nov;60(2):159-67. doi: 10.1016/0304-3835(91)90223-5.
In this study, we asked whether cholesterol contents were specifically correlated with cellular sensitivity to hyperthermia. To examine this possibility, we employed two isogenic mammalian cell lines, Chinese hamster V79 cell line and its amphotericin B-resistant (AMBr) cell line. AMBr cells had a decreased content of membrane sterols in comparison with V79 cells. Clonogenic assays showed that AMBr cells were more sensitive to hyperthermic treatment at 45 degrees C than V79 cells. Cholesterol contents were increased in AMBr cells by exposure to liposomes containing 1:1 lecithin-cholesterol, and the sterol level was comparable to that of V79 cells. In comparison with untreated AMBr cells, AMBr cells were more resistant to hyperthermia at 45 degrees C when incubated with liposomes containing cholesterol. Treatment of V79 cells with oxygenated sterol, a potent inhibitor of endogeneous sterol synthesis, sensitized the hyperthermic cytotoxicity. Our present data present the hypothesis that cellular cholesterol contents are closely correlated with cellular heat toxicity.
在本研究中,我们探讨了胆固醇含量是否与细胞对热疗的敏感性存在特定关联。为检验这种可能性,我们使用了两种同基因哺乳动物细胞系,中国仓鼠V79细胞系及其抗两性霉素B(AMBr)细胞系。与V79细胞相比,AMBr细胞的膜固醇含量降低。克隆形成试验表明,AMBr细胞在45℃热疗处理下比V79细胞更敏感。通过暴露于含有1:1卵磷脂 - 胆固醇的脂质体,AMBr细胞中的胆固醇含量增加,且固醇水平与V79细胞相当。与未处理的AMBr细胞相比,当与含胆固醇的脂质体一起孵育时,AMBr细胞在45℃下对热疗更具抗性。用含氧固醇(内源性固醇合成的有效抑制剂)处理V79细胞,可增强热疗的细胞毒性。我们目前的数据提出了一个假设,即细胞胆固醇含量与细胞热毒性密切相关。