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

Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway
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DOI:
10.1007/s13277-016-5013-2
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发表时间:
2016-08-01
期刊:
影响因子:
--
通讯作者:
Peng, Yan-hui
Peng, Yan-hui
中科院分区:
其他
文献类型:
--
作者:
Bao, Lei;Liu, Feng;Peng, Yan-hui

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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不清楚。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其机制。在这项体外研究中,SGC-7901 细胞用系列浓度的 Nar 处理。我们的数据表明,Nar 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孵育后细胞迁移和侵袭能力也显着降低,MMP2和MMP9的表达显着下调。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 cleaved 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,并且通过 Nar 和 AKT 抑制剂 LY294002 的联合治疗可以轻度增强这种抑制作用。总之,我们的研究证实Nar可以抑制SGC-7901细胞的增殖、迁移和侵袭并诱导细胞凋亡,Nar可能为治疗胃癌提供新的潜在治疗策略。
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.