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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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Tumor Biology

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.

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Abbreviations

Nar:

Naringenin

PCNA:

Proliferating cell nuclear antigen

MMPs:

Matrix metalloproteinases

MAPK:

Mitogen-activated kinase

MTT:

3-(4,5-Dimethyl-2-yl)-2,5-diphenyltetrazolium bromide

FBS:

Fetal bovine serum

ECL:

Enhanced chemiluminescence

FACS:

Fluorescence activated cell sorting

ECM:

Extracellular matrix

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Authors and Affiliations

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

    Lei Bao, Yong Li & Bi-bo Tan

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

    Feng Liu

  3. Third Department of General Surgery, Hebei General Hospital, 348 He-Ping West St., Shijiazhuang, 050051, China

    Huai-bin Guo, Wan-xing Zhang & Yan-hui Peng

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  1. Lei Bao
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  2. Feng Liu
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  3. Huai-bin Guo
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  4. Yong Li
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Correspondence to Yong Li.

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Bao, L., Liu, F., Guo, Hb. et al. Naringenin inhibits proliferation, migration, and invasion as well as induces apoptosis of gastric cancer SGC7901 cell line by downregulation of AKT pathway. Tumor Biol. 37, 11365–11374 (2016). https://doi.org/10.1007/s13277-016-5013-2

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  • DOI: https://doi.org/10.1007/s13277-016-5013-2

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