Palayoor S T, Bump E A, Calderwood S K, Bartol S, Coleman C N
Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 02215, USA.
Clin Cancer Res. 1998 Mar;4(3):763-71.
Recent clinical observations indicate that ibuprofen may alleviate the radiation-induced dysuria that almost invariably occurs during radiation therapy for prostate cancer. Because the use of ibuprofen could consequently become common during radiation therapy for prostate cancer, we have been interested in the potential interactions between ibuprofen and ionizing radiation on prostate tumor cells. The effects of gamma-irradiation and/or ibuprofen on PC3 and DU-145 human prostate carcinoma cells were evaluated in vitro using three model systems. Clonogenic survival was determined by plating cells 24 h after treatment of nearly confluent monolayers. Analysis of cell growth, cell detachment, and apoptotic cell death was carried out over a period of up to 9 days after treatment of PC3 and DU-145 monolayers. The effect of ibuprofen and/or radiation was also probed by observing the inhibition of growth of established PC3 and DU-145 colonies that were treated on the 14th day of colony growth. Ibuprofen enhanced the radiation response of prostate cancer cells in all three in vitro models. Both the cytotoxic and radiosensitizing effects of ibuprofen seem to require concentrations that are higher than those reported to inhibit prostaglandin synthesis, suggesting that other molecular mechanisms may be responsible for ibuprofen cytotoxicity.
近期的临床观察表明，布洛芬可能会缓解前列腺癌放射治疗期间几乎必然出现的放射性排尿困难。由于布洛芬在前列腺癌放射治疗期间的使用可能因此变得普遍，我们一直对布洛芬与电离辐射对前列腺肿瘤细胞的潜在相互作用感兴趣。使用三种模型系统在体外评估了γ射线照射和/或布洛芬对PC3和DU - 145人前列腺癌细胞的影响。通过在接近汇合的单层细胞处理24小时后接种细胞来确定克隆形成存活率。在PC3和DU - 145单层细胞处理后的长达9天时间内进行细胞生长、细胞脱离和凋亡性细胞死亡分析。通过观察在集落生长第14天处理的已建立的PC3和DU - 145集落的生长抑制情况，也探究了布洛芬和/或辐射的作用。在所有三种体外模型中，布洛芬均增强了前列腺癌细胞的辐射反应。布洛芬的细胞毒性和放射增敏作用似乎都需要高于据报道可抑制前列腺素合成的浓度，这表明其他分子机制可能是布洛芬细胞毒性的原因。
