Toosendanin suppresses oncogenic phenotypes of human gastric carcinoma SGC‑7901 cells partly via miR‑200a‑mediated downregulation of β-catenin pathway

Wang,Ge; Huang,Yan-Xia; Zhang,Rui; Hou,Li-Dan; Liu,Hui; Chen,Xiao-Yu; Zhu,Jin-Shui; Zhang,Jing

doi:10.3892/ijo.2017.4139

Toosendanin suppresses oncogenic phenotypes of human gastric carcinoma SGC‑7901 cells partly via miR‑200a‑mediated downregulation of β-catenin pathway

Authors:
- Ge Wang
- Yan-Xia Huang
- Rui Zhang
- Li-Dan Hou
- Hui Liu
- Xiao-Yu Chen
- Jin-Shui Zhu
- Jing Zhang
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Affiliations: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: September 27, 2017 https://doi.org/10.3892/ijo.2017.4139
Pages: 1563-1573

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Abstract

Aberrant activation of β-catenin signaling due to low expression of miR‑200a is found in gastric carcinoma (GC) tissues promoting GC evolution. Toosendanin (TSN) has exhibited antitumor effects on various human cancer cells, but its influence on GC is largely unidentified. The potential roles of TSN on GC cells were examined and it was found that TSN inhibited growth, migration, invasion and TGF‑β1-induced epithelial-mesenchymal transition (EMT) and induced cell cycle arrest and apoptosis in SGC‑7901 cells which were most sensitive to TSN among various GC cell lines. TSN also inactivated β-catenin pathway in SGC‑7901 cells and the above effects were reversed following induction of β-catenin overexpression. Moreover, TSN facilitated the level of miR‑200a which targets β-catenin and miR‑200a silencing attenuated the antitumor effects of TSN on SGC‑7901 cells. Nonetheless, knockdown of miR‑200a did not relieve the suppressive effects of TSN on p‑AKT, p‑ERK and p‑GSK3β which were upstream regulators of β-catenin. In addition, TSN administration inhibited growth and liver metastasis of orthotopically implanted SGC‑7901 tumors in vivo through miR‑200a‑mediated β-catenin pathway. Our data suggest that TSN may suppress oncogenic phenotypes of human GC cells partly via miR‑200a/β-catenin axis. Hence, TSN may have a promising chemotherapeutic activity for GC therapy.

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