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

Inhibition of Hes1 enhances lapatinib sensitivity in gastric cancer sphere-forming cells. Oncol Lett. 2017 Oct;14(4):3989-3996 Authors: Li L, Li Y, Wang L, Wu Z, Ma H, Shao J, Li D, Yu H, Nian W, Wang D 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...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research