Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells.
Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells.
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塞来昔布通过 PI3K/Akt 信号通路调节 SGC-7901 胃癌细胞凋亡和自噬
DOI：
10.3892/ijmm.2014.1713
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发表时间：
2014-06
影响因子：
5.4
通讯作者：
Zhou YN
中科院分区：
文献类型：
--
作者：
Liu M;Li CM;Chen ZF;Ji R;Guo QH;Li Q;Zhang HL;Zhou YN
胃癌是世界上最常见的恶性肿瘤之一，通常预后差，生存率低。先前的研究已经调查了塞来昔布的化学预防作用。在本研究中，SGC-7901人胃癌细胞系被用来研究塞来昔布的化学预防机制。MTT法检测细胞增殖抑制率，TUNEL法和流式细胞术检测细胞凋亡，透射电镜观察细胞超微结构变化。采用定量逆转录-聚合酶链反应（qRT-PCR）检测Akt、caspase-8和-9的mRNA表达，采用蛋白质印迹法检测p-Akt、caspase-8和-9。结果表明，塞来昔布对胃癌细胞株SGC-7901的增殖有明显的抑制作用，并呈时间和剂量依赖性。此外，塞来昔布诱导细胞凋亡，如典型的凋亡小体、自噬体和凋亡率增加所证实。结果发现，塞来昔布治疗后，Akt mRNA的表达没有显着改变，而p-Akt蛋白水平以时间和剂量依赖性的方式下降。此外，相对于时间和剂量依赖性效应，caspase-8和-9 mRNA表达显著增加，而procaspase-8和-9蛋白表达降低。这些结果表明塞来昔布通过PI 3 K/Akt信号通路诱导胃癌细胞凋亡和自噬。此外，我们的研究结果表明塞来昔布通过线粒体和死亡受体途径诱导胃癌细胞凋亡，这为塞来昔布的化学预防行为及其在癌症治疗中的用途提供了更多了解。
Gastric cancer, one of the most common malignancies worldwide, typically has a poor prognosis and poor survival rate. Previous studies have investigated the chemopreventive effect of celecoxib. In the present study, the SGC-7901 human gastric cancer cell line was utilized to examine the chemopreventive mechanisms of celecoxib. The inhibition of cell proliferation was determined using MTT assay, cell apoptosis was monitored by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and flow cytometry, and cell ultrastructural changes were assessed via transmission electron microscopy. The mRNA expression of Akt, caspase-8 and -9 was examined using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) and p-Akt, procaspase-8 and -9 were analyzed via western blotting. The results showed that celecoxib inhibited the proliferation of SGC-7901 cells in a time- and dose-dependent manner. Additionally, celecoxib induced apoptosis as substantiated by typical apoptotic bodies, autophagosomes and an increased apoptotic rate. It was found that following celecoxib treatment, Akt mRNA expression was not significantly altered, and that p-Akt protein levels decreased in a time- and dose-dependent manner. Additionally, caspase-8 and -9 mRNA expression was significantly increased, while procaspase-8 and -9 protein expression decreased relative to the time- and dose-dependent effects. These results demonstrated that celecoxib induced apoptosis and autophagy of gastric cancer cells in vitro through the PI3K/Akt signaling pathway. Moreover, our findings suggested that celecoxib induces apoptosis in gastric cancer cells through the mitochondrial and death receptor pathways, providing additional understanding regarding the chemopreventive behaviors of celecoxib and its uses in cancer therapy.
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DOI：
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发表时间：
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影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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