Storm F K, Roe D J, Hildebrand-Zanki S, Worth G D, Morton D L, Kern D H
Surgery. 1983 Aug;94(2):376-83.
We found that human malignant melanoma cells had varying thermal sensitivity and that some exhibited natural thermal resistance, a heretofore unrecognized phenomenon. Samples of 73 melanoma cell suspensions were heated at 42 degrees C for 1 hour before plating in the soft agar clonogenic assay or the thymidine assay for proliferating cells. We observed greater than 75% cell kill after hyperthermia in 39 (53%) tumors. Native thermal resistance was apparent in 17 (23%) tumors and growth enhancement in 17 (23%) at this temperature and exposure time. We postulated that prostaglandin, known to protect stomach mucosa against thermal injury, has a role in stabilizing the tumor cell membrane exposed to heat. Three melanoma cell lines known to be thermosensitive were heated to 42 degrees C without and with exogenous prostaglandin E2 (PGE2). The survival of colony-forming cells was increased in all three lines in the presence of 30 microM PGE2. A naturally thermoresistant cell line was exposed to 1 microgram/ml indomethacin for 24 hours before hyperthermic treatment. The survival of colony-forming cells was significantly decreased compared to cells not treated with indomethacin. The addition of 30 microM of exogenous PGE2 to indomethacin-treated cells reestablished thermal resistance. These preliminary data suggest that some tumor cells synthesize prostaglandins to render the cell thermoresistant. Treatment with indomethacin blocks prostaglandin synthesis and induces thermosensitivity. These discoveries may have important clinical applications for hyperthermia treatment of human cancers.
我们发现人类恶性黑色素瘤细胞具有不同的热敏感性，并且一些细胞表现出天然的热抗性，这是一种迄今未被认识的现象。在进行软琼脂克隆形成试验或用于增殖细胞的胸苷试验接种之前，将73份黑色素瘤细胞悬液样本在42℃加热1小时。我们观察到，在39个（53%）肿瘤中，热疗后细胞杀伤率超过75%。在这个温度和暴露时间下，17个（23%）肿瘤表现出天然热抗性，17个（23%）表现出生长增强。我们推测，已知可保护胃黏膜免受热损伤的前列腺素在稳定受热的肿瘤细胞膜方面发挥作用。将三种已知对热敏感的黑色素瘤细胞系分别在不添加和添加外源性前列腺素E2（PGE2）的情况下加热至42℃。在存在30微摩尔PGE2的情况下，所有三个细胞系中集落形成细胞的存活率均有所提高。在热疗前，将一个天然热抗性细胞系暴露于1微克/毫升吲哚美辛24小时。与未用吲哚美辛处理的细胞相比，集落形成细胞的存活率显著降低。向用吲哚美辛处理的细胞中添加30微摩尔外源性PGE2可重新建立热抗性。这些初步数据表明，一些肿瘤细胞合成前列腺素以使细胞具有热抗性。用吲哚美辛治疗可阻断前列腺素合成并诱导热敏感性。这些发现可能对人类癌症的热疗具有重要的临床应用价值。
