Nutlin-3-induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis through Repression of Akt1/Wnt Signaling.

Nutlin-3-induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis through Repression of Akt1/Wnt Signaling. Oncol Res. 2019 Mar 04;: Authors: Wang M, Wang X, Li Y, Xiao Q, Cui XH, Xiao GD, Wang JC, Xu CW, Ren H, Liu D Abstract To investigate the potential biological activities of nutlin-3 (N-3) in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC)stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. N-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with N-3 and then treated with either an Akt1 activator or shRNA-GSK3β, to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels of GSK3β and p-Akt1 in patients with NSCLC and determined their potential association with survival data using Kaplan-Meier plots and CBIOTAL. Increased p53 expression stimulated the induction of apoptosis by axitinib and promoted asymmetric cell division (ACD) of NSCLC CSCs. The repression of Akt phosphorylation induced by N-3 promoted the ACD of lung CSCs, decreasing the proportion of the stem cell population. In addition to the induction of apoptosis by axitinib through inhibition of Wnt signaling, N-3 treatment further enhanced axitinib-induced apoptosis by inhibiting Akt...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research