Wu Xiaoxue, Xu Yundan, Zhu Biran, Liu Qiang, Yao Qunfeng, Zhao Gang
Department of Biotechnology, School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
Department of Medical Biology, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, Hubei 430065, P.R. China.
Oncol Lett. 2018 Sep;16(3):2949-2956. doi: 10.3892/ol.2018.9045. Epub 2018 Jun 28.
The aim of the present study was to investigate the effect of resveratrol on apoptosis in SGC-7901 gastric cancer cells and its molecular mechanisms of action. Following resveratrol treatment, the inhibition rate of SGC-7901 cells was determined using an MTT assay. The morphological changes in apoptosis were observed by fluorescence microscopy based on acridine orange/ethidium bromide double staining. Furthermore, cell cycle and apoptosis were detected using flow cytometry, and the expression levels of nuclear factor κB (NF-κB) as well as apoptosis-associated proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and cleaved caspase-8] were analyzed by western blotting. The results of the present study indicated that resveratrol was able to significantly inhibit the viability of SGC-7901 cells in a dose- and time-dependent manner. When treated with 200 µM resveratrol, the inhibition rate of SGC-7901 cells reached ~50%. In the presence of resveratrol, the proportion of apoptotic cells was also increased in a dose-dependent manner. Flow cytometry revealed that resveratrol induced S-phase arrest of SGC-7901 cells. When treated with 50, 200 and 400 µM resveratrol, the proportions of SGC-7901 cells in the S-phase were respectively increased to 33.8±2.42, 60.01±2.43 and 56.05±2.67%, compared with 25.62±3.29% for the control group cells in S-phase. Additionally, the levels of the pro-apoptotic proteins Bax, cleaved caspase-3 and cleaved caspase-8 were upregulated in a dose-dependent manner, whereas the level of the anti-apoptotic protein Bcl-2 was downregulated dose-dependently. Importantly, the activation of NF-κB (p65) was evidently decreased following treatment with resveratrol compared with in the control group. In conclusion, the results of the present study revealed that resveratrol was able to inhibit viability and induce apoptosis in SGC-7901 cells by suppressing NF-κB activation. Therefore, resveratrol may be considered as a potential drug candidate for the treatment of gastric cancer.
本研究旨在探讨白藜芦醇对SGC - 7901胃癌细胞凋亡的影响及其分子作用机制。白藜芦醇处理后,采用MTT法测定SGC - 7901细胞的抑制率。基于吖啶橙/溴化乙锭双重染色,通过荧光显微镜观察凋亡的形态学变化。此外,使用流式细胞术检测细胞周期和凋亡情况,并通过蛋白质免疫印迹法分析核因子κB(NF - κB)以及凋亡相关蛋白[B细胞淋巴瘤2(Bcl - 2)、Bcl - 2相关X蛋白(Bax)、裂解的半胱天冬酶 - 3和裂解的半胱天冬酶 - 8]的表达水平。本研究结果表明,白藜芦醇能够以剂量和时间依赖性方式显著抑制SGC - 7901细胞的活力。当用200 μM白藜芦醇处理时,SGC - 7901细胞的抑制率达到约50%。在白藜芦醇存在下,凋亡细胞的比例也呈剂量依赖性增加。流式细胞术显示白藜芦醇诱导SGC - 7901细胞的S期阻滞。当用50、200和400 μM白藜芦醇处理时,SGC - 7901细胞S期的比例分别增加到33.8±2.42%、60.01±2.43%和56.05±2.67%,而对照组细胞S期的比例为25.62±3.29%。此外,促凋亡蛋白Bax、裂解的半胱天冬酶 - 3和裂解的半胱天冬酶 - 8的水平呈剂量依赖性上调,而抗凋亡蛋白Bcl - 2的水平呈剂量依赖性下调。重要的是,与对照组相比,白藜芦醇处理后NF - κB(p65)的激活明显降低。总之,本研究结果表明白藜芦醇能够通过抑制NF - κB激活来抑制SGC - 7901细胞的活力并诱导其凋亡。因此,白藜芦醇可被视为治疗胃癌的潜在候选药物。