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柚皮素通过下调AKT通路抑制胃癌SGC7901细胞系的增殖、迁移和侵袭,并诱导其凋亡。

Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway.

作者信息

Bao Lei, Liu Feng, Guo Huai-Bin, Li Yong, Tan Bi-Bo, Zhang Wan-Xing, Peng Yan-Hui

机构信息

Department of General Surgery, The Fourth Affiliated Hospital, Hebei Medical University, No. 12, Jian-Kang Road, Shijiazhuang, 050011, China.

Department of Gastroenterology, The Third Hospital of Shijiazhuang City, 15 Sports St., Shijiazhuang, China.

出版信息

Tumour Biol. 2016 Aug;37(8):11365-74. doi: 10.1007/s13277-016-5013-2. Epub 2016 Mar 10.

DOI:10.1007/s13277-016-5013-2
PMID:26960693
Abstract

The preliminary anti-cancer activity of Naringenin (Nar) has been proven in several cancers. However, the therapeutic activity of Nar on gastric cancer SGC-7901 cell line is not yet well understood. The aim of the present study was to investigate the effect and mechanisms of Nar on proliferation, apoptosis, migration, and invasion of SGC-7901 cells. In this in vitro study, SGC-7901 cells were treated with Nar at serial concentrations. Our data showed that Nar efficiently inhibited SGC-7901 cell proliferation in a time- and concentration-dependent manner, as well as downregulated proliferating cell nuclear antigen (PCNA) levels in a concentration-dependent manner. Meanwhile, the cell migration and invasion also dramatically decreased after Nar incubation, and the expressions of MMP2 and MMP9 were significantly downregulated. In addition, a strong proapoptotic effect was observed in the SGC-7901 cells after Nar treatment. Apoptosis-related proteins Bax and cleaved caspase-3 were up-regulated, whereas Bcl-2 and Survivin were downregulated. After administration with Nar, we found that phosphorylation of AKT was inhibited, and this inhibitory action could be mildly enhanced by the combination treatment of Nar and AKT inhibitor LY294002. In conclusion, our study confirmed that Nar could inhibit SGC-7901cell proliferation, migration, and invasion as well as induces apoptosis, and Nar might provide a new potential therapeutic strategy for treating gastric cancer.

摘要

柚皮素(Nar)的初步抗癌活性已在多种癌症中得到证实。然而,Nar对胃癌SGC - 7901细胞系的治疗活性尚未完全明确。本研究的目的是探讨Nar对SGC - 7901细胞增殖、凋亡、迁移和侵袭的影响及机制。在这项体外研究中,用不同浓度的Nar处理SGC - 7901细胞。我们的数据表明,Nar能以时间和浓度依赖性方式有效抑制SGC - 7901细胞增殖,并以浓度依赖性方式下调增殖细胞核抗原(PCNA)水平。同时,Nar处理后细胞迁移和侵袭也显著降低,MMP2和MMP9的表达明显下调。此外,Nar处理后的SGC - 7901细胞中观察到强烈的促凋亡作用。凋亡相关蛋白Bax和裂解的caspase - 3上调,而Bcl - 2和Survivin下调。给予Nar后,我们发现AKT的磷酸化受到抑制,Nar与AKT抑制剂LY294002联合处理可轻度增强这种抑制作用。总之,我们的研究证实Nar可抑制SGC - 7901细胞增殖、迁移和侵袭并诱导凋亡,Nar可能为胃癌治疗提供一种新的潜在治疗策略。

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