Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors.
Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors.
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DOI：
10.1593/tlo.10286
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发表时间：
2011-06
影响因子：
5
通讯作者：
M. Stearns;Min Wang
中科院分区：
文献类型：
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作者：
M. Stearns;Min Wang
我们已经检查了表没食子儿茶素-3-没食子酸酯（EGCG）和绿色茶提取物与紫杉烷（即，紫杉醇和多西他赛）在体外和体内阻断人前列腺PC-3 ML肿瘤细胞生长方面发挥协同活性。体外生长试验显示，EGCG、紫杉醇和多西他赛的IC（50）值分别为1.30 μM、1.33 nM和1.66 nM。由数据生成的等值线图清楚地表明，EGCG与紫杉醇或多西他赛组合在阻断肿瘤细胞生长方面具有累加效应。EGCG与紫杉烷的组合也具有增加凋亡基因（p53、p73、p21和半胱天冬酶3）的表达以及在严重联合免疫缺陷小鼠的体外和肿瘤建模研究中观察到的凋亡百分比的累加效应。肿瘤建模研究清楚地表明，腹腔内（i. p.）诱导细胞凋亡率的显著增加（TUNEL测定）并消除由腹膜内植入的PC-3 ML细胞产生的预先存在的肿瘤，使无病生存率提高到90%以上。更重要的是，在通过尾静脉静脉内注射PC-3 ML细胞后，联合治疗（每两周腹膜内）阻断了转移。在用表没食子儿茶素没食子酸酯加紫杉烷治疗的小鼠中，无病存活率从0%（未治疗的小鼠）增加到治疗的小鼠中的70%至80%以上。综上所述，这些数据首次证明，EGCG与紫杉烷的组合可以提供晚期前列腺癌的新的治疗方法。
We have examined whether epigallocatechin-3-gallate (EGCG), and extract of green tea, in combination with taxane (i.e., paclitaxel and docetaxel), exerts a synergistic activity in blocking human prostate PC-3ML tumor cell growth in vitro and in vivo. Growth assays in vitro revealed that the IC(50) values were ∼30 µM, ∼3 nM, and ∼6 nM, for EGCG, paclitaxel and docetaxel, respectively. Isobolograms generated from the data clearly indicated that EGCG in combination with paclitaxel or docetaxel had an additive effect in blocking tumor cell growth. EGCG combined with taxane also had an additive effect to increase the expression of apoptotic genes, (p53, p73, p21, and caspase 3) and the percent apoptosis observed in vitro and in tumor modeling studies in severe combined immunodeficient mice. The tumor modeling studies clearly showed that EGCG plus taxane injected intraperitoneally (i.p.) induced a significant increase in apoptosis rates (TUNEL assays) and eliminated preexisting tumors generated from PC-3ML cells implanted i.p., increasing disease-free survival rates to greater than 90%. More importantly, the combination therapy (i.p. biweekly) blocked metastases after intravenous injection of PC-3ML cells through the tail vein. In mice treated with EGCG plus taxane, the disease-free survival rates increased from 0% (in untreated mice) to more than 70% to 80% in treated mice. Taken together, these data demonstrate for the first time that EGCG in combination with taxane may provide a novel therapeutic treatment of advanced prostate cancer.