Yan Sen-Xiang, Ejima Yasuo, Sasaki Ryohei, Zheng Shu-Sen, Demizu Yusuke, Soejima Toshinori, Sugimura Kazuro
Department of Radiology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Asian J Androl. 2004 Dec;6(4):285-90.
To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells.
DU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting.
Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This G2/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21 cip1 levels with increasing genistein concentrations.
Genistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.
研究染料木黄酮与电离辐射（IR）联合使用对前列腺DU145癌细胞的影响。
实验采用雄激素非依赖性人前列腺癌细胞系DU145。采用克隆形成试验比较单独使用染料木黄酮以及与分级IR联合使用后DU145细胞的存活率。通过DNA梯状条带和TUNEL染色检测细胞凋亡。通过流式细胞术观察细胞周期变化，通过免疫印迹法检测相关蛋白表达。
克隆形成试验表明，即使在低至中等浓度下，染料木黄酮也能增强DU145细胞的放射敏感性。用IR和/或染料木黄酮处理24小时后，高浓度染料木黄酮组可见明显凋亡，且与IR关系不大。72小时时，低浓度染料木黄酮处理组也出现凋亡，尤其是与IR联合使用时。IR和染料木黄酮均导致G2/M期细胞周期阻滞，二者联合使用进一步增加了处于G2/M期的DU145细胞数量。这种G2/M期阻滞在72小时时基本维持，同时伴随着凋亡增加和超二倍体细胞群体增多。细胞周期相关蛋白分析显示，细胞周期蛋白B1呈双相变化，细胞分裂周期蛋白2变化不太明显，但随着染料木黄酮浓度增加，p21 cip1水平稳定升高。
染料木黄酮增强了DU145前列腺癌细胞的放射敏感性。其机制可能与凋亡增加、细胞周期阻滞延长及损伤修复受损有关。
