Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Gu,Hongbing; Li,Xu; Zhou,Congzhi; Wen,Yugang; Shen,Yang; Zhou,Lisheng; Li,Jikun

doi:10.3892/ol.2015.3032

Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Authors:
- Hongbing Gu
- Xu Li
- Congzhi Zhou
- Yugang Wen
- Yang Shen
- Lisheng Zhou
- Jikun Li
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Affiliations: Department of Surgery, First People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, P.R. China
Published online on: March 12, 2015 https://doi.org/10.3892/ol.2015.3032
Pages: 1997-2002
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Excessive activation of the hedgehog (Hh) signaling pathway is important in a variety of human cancer cell types, including gastric cancer. However, the underlying mechanisms of the Hh signaling pathway in inducing gastric tumorigenesis and its downstream target genes are largely unknown. In the present study, the inhibitory effect of cyclopamine on the Hh signaling pathway was investigated in the human gastric cancer AGS cell line. It was identified that cyclopamine treatment inhibited the proliferation, migration and invasion of the AGS cells in a dose‑ and time‑dependent manner, and resulted in the downregulation of a number of key Hh signaling pathway‑associated factors [glioma‑associated oncogene homolog 1, C‑X‑C chemokine receptor type 4 and transforming growth factor (TGF)‑β1] at the RNA and protein levels. Furthermore, the secretion of TGF‑β1 was significantly reduced following the administration of cyclopamine to the AGS cells. The results of the present study provided insight into the mechanisms by which the Hh signaling pathway regulates gastric cancer formation and identified the Hh signaling pathway as a potential novel therapeutic target in human gastric cancer.

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