Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner.
Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner.
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DOI：
10.1371/journal.pone.0070627
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Yang Q;Wang B;Zang W;Wang X;Liu Z;Li W;Jia J
白藜芦醇是一种天然存在的多酚类化合物，已被报道通过影响多种分子靶点发挥抗癌活性。本研究旨在探讨白藜芦醇对胃癌的作用及其机制。我们发现，白藜芦醇抑制胃癌细胞的增殖，并呈剂量依赖性。在25和50 µM浓度下，白藜芦醇抑制胃癌细胞的细胞活力，并降低胃癌细胞的克隆形成潜力。白藜芦醇处理使胃癌细胞停滞在G1期，并导致衰老而不是凋亡。细胞周期和衰老途径的调节因子，包括细胞周期蛋白D1，细胞周期蛋白依赖性激酶（CDK 4和6），p21和p16，被白藜芦醇处理失调。白藜芦醇对胃癌的抑制作用也在裸鼠移植瘤模型中得到了验证。白藜芦醇（40 mg/kg/d）对胃癌的发展具有抑制作用，并显著降低裸鼠肿瘤标本中Ki 67阳性细胞的比例。白藜芦醇处理后，衰老的诱导以及参与细胞周期和衰老途径的调节因子表达的变化与我们在体外观察到的相似。然而，Sirtuin（Sirt）1的耗竭逆转了白藜芦醇在体外和体内的上述作用。我们的研究结果提示白藜芦醇以Sirt 1依赖的方式抑制胃癌的发生，为白藜芦醇应用于胃癌预防和治疗的可能性提供了详细的证据。
Resveratrol, a naturally occurring polyphenolic compound, has been reported to exert anticancer activity by affecting diverse molecular targets. In this study, we examined the effects and the underlying mechanisms of resveratrol on gastric cancer. We found that resveratrol inhibited the proliferation of gastric cancer cells in a dose-dependent manner. At the concentration of 25 and 50 µM, resveratrol inhibited the cell viability and diminished the clonogenic potential of gastric cancer cells. Resveratrol treatment arrested gastric cancer cells in the G1 phase and led to senescence instead of apoptosis. Regulators of the cell cycle and senescence pathways, including cyclin D1, cyclin-dependent kinase (CDK4 and 6), p21 and p16, were dysregulated by resveratrol treatment. The inhibitory effects of resveratrol on gastric cancer were also verified in vivo using a nude mice xenograft model. Resveratrol (40 mg/kg/d) exerted inhibitory activities on gastric cancer development and significantly decreased the fractions of Ki67-positive cells in the tumor specimens from the nude mice. After resveratrol treatment, the induction of senescence and the changes in the expression of the regulators involved in the cell cycle and senescence pathways were similar to what we observed in vitro. However, the depletion of Sirtuin (Sirt)1 reversed the above-described effects of resveratrol both in vitro and in vivo. Our data suggest that resveratrol inhibits gastric cancer in a Sirt1-dependent manner and provide detailed evidence for the possibility of applying resveratrol in gastric cancer prevention and therapy.
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影响因子：
4.8
作者：
Pacholec, Michelle;Bleasdale, John E.;Ahn, Kay
通讯作者：
Ahn, Kay
影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars
DOI：
10.1111/j.1749-6632.2010.05853.x
发表时间：
2011-01-01
期刊：
RESVERATROL AND HEALTH
影响因子：
--
作者：
Patel, Ketan R.;Scott, Edwina;Brown, Karen
通讯作者：
Brown, Karen
影响因子：
5.7
作者：
Bai, Yu;Mao, Qi-Qi;Xie, Li-Ping
通讯作者：
Xie, Li-Ping
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido