Shi Ting, Liou Louis S, Sadhukhan Provash, Duan Zhong-Hui, Novick Andrew C, Hissong John G, Almasan Alexandru, DiDonato Joseph A
Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Cancer Biol Ther. 2004 Sep;3(9):882-8. doi: 10.4161/cbt.3.9.1056. Epub 2004 Sep 21.
Studies have shown that Resveratrol (RE) can inhibit cancer initiation, promotion, and progression. However the gene expression profile in renal cell carcinoma (RCC) in response to RE treatment has never been reported. To understand the potential anticancer effect of RE on RCC at molecular level, we profiled and analyzed the expression of 2059 cancer-related genes in a RCC cell line RCC54 treated with RE. Biological functions of 633 genes were annotated based on biological process ontology and clustered into functional categories. Twenty-nine highly differentially expressed genes in RE treated RCC54 were identified and the potential implications of some gene expression alterations in RCC carcinogenesis were identified. RE was also shown to inhibit cell growth and induce cell death of RCC cells. The expression alterations of selected genes were validated using reverse transcription polymerase chain reaction. In addition, the gene expression profiles under different RE treatments were analyzed and visualized using singular value decomposition. The findings from this study support the hypothesis that RE induces differential expression of genes that are directly or indirectly related to the inhibition of RCC cell growth and induction of RCC cell death. In addition, it is apparent that the gene expression alterations due to RE treatment depend strongly on RE concentration. This study provides a general understanding of the overall genetic response of RCC54 to RE treatment and yields insights into the understanding of the cancer preventive mechanism of RE in RCC.
研究表明，白藜芦醇（RE）可抑制癌症的起始、促进和进展。然而，肾细胞癌（RCC）对RE治疗的基因表达谱尚未见报道。为了在分子水平上了解RE对RCC的潜在抗癌作用，我们对用RE处理的RCC细胞系RCC54中2059个癌症相关基因的表达进行了分析。基于生物学过程本体对633个基因的生物学功能进行了注释，并将其聚类为功能类别。我们鉴定了在RE处理的RCC54中29个高度差异表达的基因，并确定了RCC致癌过程中一些基因表达改变的潜在影响。RE还被证明可抑制RCC细胞的生长并诱导其死亡。使用逆转录聚合酶链反应对所选基因的表达改变进行了验证。此外，使用奇异值分解对不同RE处理下的基因表达谱进行了分析和可视化。本研究结果支持以下假设：RE诱导与抑制RCC细胞生长和诱导RCC细胞死亡直接或间接相关的基因差异表达。此外，很明显，RE处理引起的基因表达改变强烈依赖于RE浓度。本研究提供了对RCC54对RE治疗的整体遗传反应的总体理解，并有助于深入了解RE在RCC中的癌症预防机制。
