Specific inhibitor of Notch ‑3 enhances the sensitivity of NSCLC cells to gemcitabine.

Specific inhibitor of Notch‑3 enhances the sensitivity of NSCLC cells to gemcitabine. Oncol Rep. 2018 May 16;: Authors: Hu BD, Guo J, Ye YZ, Du T, Cheng CS, Jiang Q, Liu RN, Zhang YB Abstract Notch‑3 is a receptor of the Notch signaling pathway and plays an important role in regulating self‑renewal, differentiation and apoptosis in cancer cells. Overexpression of Notch‑3 has been proved to be associated with resistance to gemcitabine (GEM) and poor patient prognosis for various malignant tumors. In the present study, two non‑small cell lung cancer (NSCLC) cell lines, H1299 and A549, were induced with GEM for two months and then were treated with various concentrations of a Notch signaling blocker, N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT), with the goal of reducing expression of Notch intracellular domain 3 (NICD3). Both cell lines were subsequently treated with either DAPT or DAPT combined with GEM and then viability, apoptosis, colony formation and cell count assays were performed. DAPT treatment effectively downregulated the expression of NICD3 in both cell lines. DAPT combined with GEM also significantly reduced the percentage of viable cells in both cell lines, while increasing the percentage of apoptotic cells, compared with GEM alone. In the clonogenicity assays, the combination of DAPT and GEM led to a decrease in clone numbers and significantly greater inhibition ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research