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首页> 外文期刊>Chinese science bulletin >Dual regulatory effects of resveratrol on activation of NF-KB and cell proliferation in human embryonal kidney 293 cells
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Dual regulatory effects of resveratrol on activation of NF-KB and cell proliferation in human embryonal kidney 293 cells

机译：白藜芦醇对人胚肾293细胞中NF-κB活化和细胞增殖的双重调控作用

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摘要

Resveratrol (3,4',5-trihydroxystilbene, Res), a naturally occurring polyphenol, exhibits antioxidant, anti-inflammatory, potential cnemopreventive and chemothera-peutic properties in preclinical studies. To further understand its potential clinical efficacy and safety, effect of Res at 10~(-9)-10~(-4) mol/L on human embryonal kidney (HEK293) cell proliferation and its potential mechanism were investigated in present study. Cell viability was detected by using trypan blue dye exclusion method. Cell cycle and apoptosis were analyzed by flow cytometry with propidium iodide stain. Activation of nuclear factor-KB (NF-KB) was determined by luciferase reporter gene assay using stably transfected HEK293/KS-1UC cells. Secretion of human interleukin-8 (hIL-8) was measured by ELISA. Our results show that HEK293 cell proliferation was significantly stimulated by 10~(-7) mol/L Res after treatment for 48 hours, or by 10~(-8)-10~(-7) mol/L Res combinated with 10 ng/mL TNFa for 24 h, but was suppressed by 10~(-4) mol/L Res with or without TNFa. Both endogenous and TNFa-induced NF-KB activation were downregulated by Res at 10~(-7) mol/L, but were upregulated at 10~(-4) mol/L. With 10~(-4) mol/L Res, the content of secreted IL-8 was increased, and apoptosis rate was increased from less than 5 percent to 10 percent, together with significant cell-cycle arrest In S phase. TNFa has coordinative effects with Res on HEK293 cell apoptosis, cell-cycle arrest and IL-8 secretion. These results indicate that Res promotes cell proliferation at low concentration through down-regulation of NF-KB activation in HEK293, but suppresses its growth at high concentration through up-regulation of NF-KB activation, increasing IL-8 and cell-cycle arrest. As resveratrol has dual regulatory effect on cell proliferation in vitro, comprehensive evaluation of its potential clinical utility is needed.
机译：白藜芦醇（3,4'，5-三羟基sti，Res）是一种天然存在的多酚，在临床前研究中表现出抗氧化，抗炎，潜在的预防和化学治疗特性。为了进一步了解其潜在的临床疗效和安全性，本研究研究了10〜（-9）-10〜（-4）mol / L的Res对人胚肾（HEK293）细胞增殖的影响及其潜在机制。通过使用锥虫蓝染料排除法检测细胞活力。通过碘化丙啶染色的流式细胞仪分析细胞周期和凋亡。使用稳定转染的HEK293 / KS-1UC细胞，通过萤光素酶报告基因测定，确定核因子KB（NF-KB）的激活。通过ELISA测量人白介素8（hIL-8）的分泌。我们的结果表明，处理48小时后，10〜（-7）mol / L Res或10 ng（10）（-8）-10〜（-7）mol / L Res联合10 ng可以显着刺激HEK293细胞的增殖。 / mL TNFa持续24 h，但在有或没有TNFa的情况下被10〜（-4）mol / L Res抑制。 Res在10〜（-7）mol / L下均内源性和TNFa诱导的NF-KB激活均下调，而在10〜（-4）mol / L时上调。在10〜（-4）mol / L Res条件下，分泌的IL-8含量增加，细胞凋亡率从不到5％提高到10％，并且细胞周期明显停滞在S期。 TNFa与Res协同作用于HEK293细胞凋亡，细胞周期停滞和IL-8分泌。这些结果表明，Res通过下调HEK293中的NF-KB激活促进低浓度下的细胞增殖，但通过上调NF-KB的激活，增加IL-8和细胞周期的阻滞来抑制其在高浓度下的生长。由于白藜芦醇对体外细胞增殖具有双重调节作用，因此需要对其潜在临床实用性进行全面评估。

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