Notch signaling molecule is involved in the invasion of MiaPaCa2 cells induced by CoCl2 via regulating epithelial‑mesenchymal transition

Chen,Ding‑Wei; Wang,Hong; Bao,Ya‑Fang; Xie,Kun

doi:10.3892/mmr.2018.8502

Notch signaling molecule is involved in the invasion of MiaPaCa2 cells induced by CoCl2 via regulating epithelial‑mesenchymal transition

Authors:
- Ding‑Wei Chen
- Hong Wang
- Ya‑Fang Bao
- Kun Xie
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Affiliations: Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China, Caihe Street Community Health Service Center, Hangzhou, Zhejiang 310016, P.R. China
Published online on: January 26, 2018 https://doi.org/10.3892/mmr.2018.8502
Pages: 4965-4972
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit‑8 assay, invasion assay, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2). Hypoxia‑inducible factor 1α (HIF‑1α) small interfering (si)RNA and Notch1 inhibitor N‑[N‑(3,5‑Difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT) were also selected to investigate these mechanisms. Data indicated that CoCl2 increased the invasion ability and altered EMT in MiaPaCa2 cells. CoCl2 regulated the expression of HIF‑1α and Notch1 in MiaPaCa2 cells. In addition, HIF‑1α siRNA inhibited the effects of CoCl2 on the expression of Notch1 and decreased Snail, EMT and invasion in MiaPaCa2 cells. DAPT increased the expression of epithelial‑cadherin and decreased the content of neural‑cadherin, Snail and invasion in MiaPaCa2 cells in the presence or absence of CoCl2. CoCl2 promoted invasion by stimulating the expression of HIF‑1α and regulating the expression of Notch1 and EMT in MiaPaCa2 cells. Targeting the Notch1 signaling molecule may be a novel treatment strategy for the prevention and treatment of pancreatic cancer.

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