Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
J Surg Res. 2013 Jan;179(1):e141-8. doi: 10.1016/j.jss.2012.02.057. Epub 2012 Mar 28.
Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma.
The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50% polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student's t-test, analysis of variance, and the Mann-Whitney rank sum test.
RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot.
Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.
白藜芦醇（RESV）是一种天然存在的化合物，可能具有前列腺癌和黑色素瘤的抗癌能力。
使用细胞测定法和异种移植模型测试 RESV 和 3,5-二羟基-4'-乙氧基反式-二苯乙烯（4-ACE）的体外和体内细胞毒性活性。使用五种前列腺癌细胞系进行体外评估。黑色素瘤细胞系（杜克黑色素瘤 738 [DM738]）和前列腺癌细胞系 CWR22 用于体内实验。将小鼠随机分配到带有 200 μL RESV（250 mg/mL）、4-ACE（335 mg/mL）或载体（50%二甲基亚砜，50%聚乙二醇）的渗透微型泵中。通过高效液相色谱法用二极管阵列检测计算血清药物和代谢物水平。对处理过的肿瘤进行 Western 印迹。使用学生 t 检验、方差分析和曼-惠特尼秩和检验分析结果。
RESV 和 4-ACE 在所有测试的前列腺癌细胞系中均表现出时间和剂量依赖性的细胞毒性。与对照组相比，四种 RESV 处理的细胞系和两种 4-ACE 处理的细胞系在 24 小时时间点观察到增强的生长（Ps < 0.048）。在体内，无论是 DM738（P = 0.555，P = 0.562）还是 CWR22（P = 0.166，P = 0.811）异种移植，用任何药物处理的肿瘤生长或死后肿瘤重量均无差异。对于任何治疗组，血清药物水平均与肿瘤生长率无关（所有 Ps > 0.11）。通过 Western 印迹显示处理过的肿瘤的蛋白质发生变化。
尽管体外数据很有希望，但 RESV 和 4-ACE 作为单一药物在治疗前列腺癌和黑色素瘤方面的潜力有限。
