Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, PR China.
Int J Mol Med. 2013 Mar;31(3):621-7. doi: 10.3892/ijmm.2013.1237. Epub 2013 Jan 10.
Resveratrol (trans-3,4',5-trihydroxystilbene) has been shown to exert potent anticancer effects on various types of cancer through its anti-proliferative, anti-angiogenic, antioxidant and pro-apoptotic functions. There is still a lack of experimental evidence regarding whether resveratrol has potential anticancer activity in human nasopharyngeal carcinoma (NPC) cells. The purpose of this study was to explore the anticancer activity of resveratrol in human NPC cells both in vitro and in vivo. Our results indicated that treatment with resveratrol led to a time- and dose-dependent decrease in cell proliferation in NPC cells. A dose-dependent increase in apoptosis in response to resveratrol treatment was also observed in NPC cells. Flow cytometric analysis showed that treatment of NPC cells with resveratrol led to cell cycle arrest at the S and G2/M phases. Mechanistically, resveratrol treatment downregulated the expression of Bcl-2 and hypoxia-inducible factor-1α (HIF-1α) proteins and upregulated the expression of caspase-3 protein. In addition, resveratrol treatment also significantly decreased the phosphorylation levels of Akt1, p70S6K and p-4E-BP-1 and the protein expression of several cyclins involved in cell cycle regulation. In vivo studies further showed that resveratrol was able to significantly inhibit the growth of NPC tumor xenografts in nude mice. Collectively, our findings suggest that resveratrol exerts potent anti-prolife-rative and pro-apoptotic effects on human NPC cells possibly through interfering with the pAkt1/p70S6K signaling pathways, thus it may potentially be developed as an effective agent for chemoprevention and chemotherapy of human NPC.
白藜芦醇(反式-3,4',5-三羟基二苯乙烯)已被证明通过其抗增殖、抗血管生成、抗氧化和促凋亡作用对多种类型的癌症具有强大的抗癌作用。关于白藜芦醇在人鼻咽癌(NPC)细胞中是否具有潜在的抗癌活性,仍然缺乏实验证据。本研究旨在探讨白藜芦醇在体外和体内对人 NPC 细胞的抗癌活性。我们的结果表明,白藜芦醇处理导致 NPC 细胞的增殖呈时间和剂量依赖性下降。还观察到 NPC 细胞对白藜芦醇处理的凋亡呈剂量依赖性增加。流式细胞术分析表明,白藜芦醇处理导致 NPC 细胞的细胞周期停滞在 S 和 G2/M 期。机制上,白藜芦醇处理下调了 Bcl-2 和缺氧诱导因子-1α(HIF-1α)蛋白的表达,并上调了 caspase-3 蛋白的表达。此外,白藜芦醇处理还显著降低了 Akt1、p70S6K 和 p-4E-BP-1 的磷酸化水平以及参与细胞周期调节的几种细胞周期蛋白的蛋白表达。体内研究进一步表明,白藜芦醇能够显著抑制裸鼠 NPC 肿瘤异种移植的生长。总之,我们的研究结果表明,白藜芦醇对人 NPC 细胞具有强大的抗增殖和促凋亡作用,可能是通过干扰 pAkt1/p70S6K 信号通路,因此它可能有潜力开发为人类 NPC 的化学预防和化疗的有效药物。