Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
J Surg Res. 2012 Jan;172(1):109-15. doi: 10.1016/j.jss.2010.07.033. Epub 2010 Aug 6.
Resveratrol (RESV) is a naturally occurring compound that possesses anti-cancer capabilities. The goal of this study was to evaluate the potential of RESV as an adjunct to chemotherapy in melanoma treatment.
The in vitro and in vivo cytotoxic activity of RESV with or without chemotherapy was tested using cellular assays and a xenograft model. Two Duke melanoma cell lines (DM738, DM443) were used for both in vivo and in vitro experiments, and two nonmalignant human fibroblast lines (NHDF, HS68) were used for in vitro cellular assays. Xenografts were randomized to treatment arms and tumors measured to evaluate response. Results were analyzed using a Student's t-test and ANOVA. Western blots were performed on in vivo tissue.
In vitro RESV significantly decreased melanoma cell viability in all lines tested (all P < 0.0001). Treatment of fibroblast cell lines revealed that RESV selectively spared NHDF and HS68 cells compared with its cytotoxic effects on melanoma cells (P < 0.0001). Treatment of malignant cells with 50 μM RESV and temozolomide (TMZ) for 72 h significantly enhanced cytotoxicity compared with treatment with TMZ alone (P < 0.0001). In vivo, however, there was no significant difference between any treatment arms (P = 0.65).
RESV shows promise as a novel therapeutic in the management of melanoma for its selective anti-tumor activity in vitro. Translating in vitro results to in vivo models has proven difficult. Barriers thought to prevent such translation are identified, and a rationale for overcoming them is discussed.
白藜芦醇（RESV）是一种天然存在的化合物，具有抗癌能力。本研究的目的是评估 RESV 作为辅助化疗治疗黑色素瘤的潜力。
使用细胞测定法和异种移植模型测试 RESV 联合或不联合化疗的体外和体内细胞毒性活性。两种杜克黑色素瘤细胞系（DM738、DM443）用于体内和体外实验，两种非恶性人成纤维细胞系（NHDF、HS68）用于体外细胞测定。异种移植物随机分配到治疗组，并测量肿瘤以评估反应。使用学生 t 检验和 ANOVA 分析结果。对体内组织进行 Western 印迹分析。
在所有测试的细胞系中，RESV 显著降低了黑色素瘤细胞的活力（均 P < 0.0001）。处理成纤维细胞系表明，与 RESV 对黑色素瘤细胞的细胞毒性作用相比，RESV 选择性地保留了 NHDF 和 HS68 细胞（均 P < 0.0001）。用 50 μM RESV 和替莫唑胺（TMZ）处理恶性细胞 72 小时，与单独用 TMZ 处理相比，显著增强了细胞毒性（均 P < 0.0001）。然而，在体内，任何治疗组之间均无显著差异（P = 0.65）。
RESV 作为一种新的治疗方法，在体外具有选择性抗肿瘤活性，有望用于黑色素瘤的治疗。将体外结果转化为体内模型证明具有挑战性。确定了阻止这种转化的障碍，并讨论了克服这些障碍的理由。
