Gastric tumor-initiating CD44+ cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT

Li,Lu‑Chun; Wang,Dong‑Lin; Wu,Yong‑Zhong; Nian,Wei‑Qi; Wu,Zhi‑Juan; Li,Yan; Ma,Hui‑Wen; Shao,Jiang‑He

doi:10.3892/ol.2015.3727

Gastric tumor-initiating CD44+ cells and epithelial-mesenchymal transition are inhibited by γ-secretase inhibitor DAPT

Authors:
- Lu‑Chun Li
- Dong‑Lin Wang
- Yong‑Zhong Wu
- Wei‑Qi Nian
- Zhi‑Juan Wu
- Yan Li
- Hui‑Wen Ma
- Jiang‑He Shao
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Affiliations: Department of Oncology, Chongqing Cancer Institute, Chongqing 400030, P.R. China, Department of Radiotherapy, Chongqing Cancer Institute, Chongqing 400030, P.R. China, Department of Galactophore, Chongqing Cancer Institute, Chongqing 400030, P.R. China
Published online on: September 18, 2015 https://doi.org/10.3892/ol.2015.3727
Pages: 3293-3299

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Abstract

It has been proposed that the Notch signaling pathway may serve a pivotal role in cellular differentiation, proliferation and apoptosis. However, the function of Notch signaling in gastric cancer stem cells (GCSCs) is largely unknown. The present study aimed to delineate the role of the Notch1 pathway in GCSCs and during epithelial‑mesenchymal transition (EMT). Flow cytometry was used to isolate CD44+ cells from the human gastric cancer cell line, MKN45. CD44+ cells displayed the characteristics of CSCs and exhibited higher Notch1 expression compared with CD44‑ cells. To investigate the role of the Notch1 pathway in GCSCs, CD44+ cells were treated with the γ‑secretase inhibitor DAPT. DAPT treatment inhibited the expression of the Notch1 downstream target Hes1 and EMT markers, suppressed the properties of CSCs and impaired the invasion and proliferation capabilities of CD44+ cells. In addition, intraperitoneal treatment with DAPT effectively inhibited the growth of CD44+ cell xenograft tumors. The present study indicated that CD44+ GCSCs possess the characteristics of CSCs and that the Notch1 pathway serves a critical role in the maintenance of CSCs and EMT.

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