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岩藻黄质通过 JAK/STAT 信号通路对人胃腺癌 MGC-803 细胞增殖和凋亡的影响。

Effects of fucoxanthin on proliferation and apoptosis in human gastric adenocarcinoma MGC-803 cells via JAK/STAT signal pathway.

机构信息

Department of pharmacology, Medical college of Wuhan University of Science and Technology, Wuhan 430080, China.

出版信息

Eur J Pharmacol. 2011 Apr 25;657(1-3):10-9. doi: 10.1016/j.ejphar.2010.12.006. Epub 2010 Dec 24.

Abstract

In this study, we investigated the anti-tumor effects and possible mechanisms of fucoxanthin, which has been reported to inhibit tumor proliferation and induce apoptosis in vitro or in vivo. Human gastric adenocarcinoma MGC-803 cells were treated with fucoxanthin (25μM, 50μM or 75μM). Data of flow cytometry revealed that fucoxanthin (50μM or 75μM) increased the ratio of cell in G2/M phase and apoptotic MGC-803 cells varying on a dose-dependent manner. Results from reverse transcriptase-polymerase chain reaction and Western blot showed that treatment with fucoxanthin (50μM or 75μM) significantly decreased the expressions of CyclinB1, survivin and STAT3 in MGC-803 cells in a dose-dependent manner both at the time of 24h and 48h. In addition, immunofluorescence microscopy analysis also revealed the suppressed expressions of CyclinB1 and survivin by fucoxanthin. After pretreatment with AG490 (the inhibitor for JAK/STAT signal pathway), the expressions of p-STAT3 and survivin remained also slightly lower than the vehicle control group. Co-treated with fucoxanthin (75μM) and AG490, the reduction on the expressions of STAT3, p-STAT3 and CyclinB1 by fucoxanthin were attenuated while that of survivin was enhanced. Taken together, fucoxanthin can down-regulate the expressions of CyclinB1 and survivin, inducing cell cycle arrest in G2/M phase, and apoptosis in MGC-803 cells. The reduction of CyclinB1 by fucoxanthin was associated with JAK/STAT signal pathway.

摘要

在这项研究中,我们研究了岩藻黄质的抗肿瘤作用及其可能的机制,已有研究报道岩藻黄质可抑制肿瘤的增殖并在体外或体内诱导细胞凋亡。用岩藻黄质(25μM、50μM 或 75μM)处理人胃腺癌 MGC-803 细胞。流式细胞术数据显示,岩藻黄质(50μM 或 75μM)以剂量依赖性方式增加细胞处于 G2/M 期和凋亡的 MGC-803 细胞的比例。逆转录-聚合酶链反应和 Western blot 的结果表明,用岩藻黄质(50μM 或 75μM)处理可显著降低 MGC-803 细胞中 CyclinB1、survivin 和 STAT3 的表达,24h 和 48h 时均呈剂量依赖性。此外,免疫荧光显微镜分析也显示岩藻黄质抑制了 CyclinB1 和 survivin 的表达。用 AG490(JAK/STAT 信号通路抑制剂)预处理后,p-STAT3 和 survivin 的表达仍略低于载体对照组。与岩藻黄质(75μM)和 AG490 共同处理时,岩藻黄质对 STAT3、p-STAT3 和 CyclinB1 表达的下调作用减弱,而 survivin 的表达增强。综上所述,岩藻黄质可下调 CyclinB1 和 survivin 的表达,诱导 MGC-803 细胞周期停滞在 G2/M 期,并诱导细胞凋亡。岩藻黄质对 CyclinB1 的下调与 JAK/STAT 信号通路有关。

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