Inhibition of Hes1 enhances lapatinib sensitivity in gastric cancer sphere-forming cells

Li,Luchun; Li,Yan; Wang,Lulu; Wu,Zhijuan; Ma,Huiwen; Shao,Jianghe; Li,Dairong; Yu,Huiqing; Nian,Weiqi; Wang,Donglin

doi:10.3892/ol.2017.6683

Inhibition of Hes1 enhances lapatinib sensitivity in gastric cancer sphere-forming cells

Authors:
- Luchun Li
- Yan Li
- Lulu Wang
- Zhijuan Wu
- Huiwen Ma
- Jianghe Shao
- Dairong Li
- Huiqing Yu
- Weiqi Nian
- Donglin Wang
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Affiliations: Department of Oncology, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing 400030, P.R. China, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing 400030, P.R. China
Published online on: July 27, 2017 https://doi.org/10.3892/ol.2017.6683
Pages: 3989-3996
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been considered that the neurogenic locus notch homolog protein (Notch) signaling pathway serves an essential role in cellular differentiation, proliferation and apoptosis. However, the function of the Notch signaling pathway in gastric cancer stem cells (GCSCs) and epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI) sensitivity remains unclear. The present study aimed to delineate the role of the Notch1 signaling pathway in GCSCs and lapatinib sensitivity. Sphere‑forming cells were separated from human gastric cancer MKN45 parental cells. The sphere‑forming cells exhibited characteristics of CSCs and higher Notch1 expression compared with that of parental cells. To investigate the role of the Notch1 signaling pathway in GCSCs, the expression of transcription factor Hes1 (Hes1) was knocked down using small interfering RNA against Hes1. It was observed that Hes1 expression was significantly downregulated in knocked down cells. The inhibition of Hes1 suppressed the properties of CSCs, as indicated by significant decreases in the expression of the transcription factor sex determining region Y‑box 2, epithelial cell adhesion molecule and the homeobox protein Nanog and reduced spheroid colony formation. In addition, epithelial-mesenchymal transition was significantly impaired in sphere‑forming cells following Hes1 knockdown. Furthermore, the inhibition of Hes1 effectively enhanced lapatinib sensitivity in sphere‑forming cells. These results suggest that sphere‑forming gastric cancer cells possess the characteristics of CSCs, and that the Notch1 signaling pathway serves an essential role in the maintenance of CSCs and lapatinib sensitivity.

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