Urologic Oncology, 2010, 28(2):170-9.

Taxol synergizes with antioxidants in inhibiting hormal refractory prostate cancer cell growth

Szu-Yuan Ping, Dah-Shyong Yu, et al

Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan, Republic of China; et al

Taxanes are chemotherapeutic agents commonly used to treat various carcinomas. Dietary antioxidants, such as vitamin E, green tea extracts, and isoflavones have been used against prostate cancer, and exhibit anticancer effects both in vitro and in vivo. We evaluated the combined effect of taxol (paclitaxel) with pyrrolidine dithiocarbamate, vitamin E, epigallocatechin gallate, and genistein in killing hormone-refractory prostate cancer cells. Those agents were tested on the hormone-refractory prostate cancer cell line PC-3, and the viability of the cells was determined using MTT {3 (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium} assay after drug treatment. PC-3 cells were sensitive to these drugs with 50% inhibitory concentrations of 0.1, 23, 220, 1122, and 260 microM, for taxol, pyrrolidine dithiocarbamate, epigallocatechin gallate, genistein, and vitamin E, respectively. Genistein, pyrrolidine dithiocarbamate, and epigallocatechin gallate showed synergistic cytotoxicity to PC-3 cells when combined with 0.01 microM taxol. Only high concentration of vitamin E showed a synergistic effect with this dose of taxol. Further study revealed that 3 combinations could induce sub-G1 phase of cell cycle, induce apoptosis, and increase caspase activity and decrease Bcl-2 expression simultaneously. In conclusion, in addition to vitamin E, incorporation of these antioxidants with taxan-based cytotoxic therapies offers encouraging strategies for combating hormone-refractory prostate cancers.

美国《泌尿外科肿瘤学》，2010年3月

紫杉醇协同抗氧化剂抑制激素难治性前列腺癌细胞的生长

平素媛，于大雄等

台湾国防医学院生命科学研究生协会等

紫杉烷类化合物是一种常用于治疗多种癌症的化疗药物。膳食抗氧化剂，例如维生素 E、 绿茶提取物和异黄酮等也曾用于防治前列腺癌，并且在体外和体内表现出抗肿瘤作用。我们评估了紫杉酚 （紫杉醇）和 硫代氨基甲酸吡咯烷、 维生素 E、 儿茶素没食子酸和染料木黄酮联合杀死激素非依赖性前列腺癌细胞的效果。在激素非依赖性的前列腺癌细胞PC-3中对这些试剂进行测试，并且在药物治疗后使用MTT 比色法测定细胞的存活率。紫杉醇、 硫代氨基甲酸吡咯烷、 儿茶素没食子酸、 染料木黄酮，维生素 E的50%抑制浓度分别为0.1、 23、 220、 1122和 260 uM，PC-3 细胞对这些药物比较敏感。染料木黄酮、 吡咯烷氨基甲酸盐和儿茶素没食子酸与 0.01 microM 紫杉醇联合使用时表现出对 PC-3 细胞的协同毒性。只有高浓度的维生素 E 与此剂量的紫杉醇才会显示出协同效应。进一步研究表明，3 组合可以同时诱导细胞周期的sub-G1 期、 诱导细胞凋亡，提高半胱氨酸蛋白酶活性，并且降低Bcl-2的 表达。总之，除了维生素E以外，这些抗氧化剂和基于紫杉醇的细胞毒疗法可以令人鼓舞地治疗激素难治性前列腺癌。