A novel small-molecule PI3K/Akt signaling inhibitor, W934, exhibits potent antitumor efficacy in A549 non-small-cell lung cancer

In this study, we explored the in-vitro and in-vivo antitumor effects of W934 on A549 non-small-cell lung cancer cells and HCT116 colorectal cancer cells. In-vitro assays showed that W934 caused an inhibition of PI3Kα kinase. W934 can significantly suppress the viability of A549 and HCT116 cells with IC50 values of 0.25 and 0.23 μmol/l, respectively. Besides, the inhibitory effects on cell migration, invasion and apoptosis were also observed after treatment of W934 for the indicated hours. According to the cell cycle analysis, W934 caused an inhibition of G0–G1 phase progression and correspondingly decreased the percentage of cells in S and G2–M phases. Results of western blotting indicated that W934 concentration dependently suppressed the activation of the PI3K/Akt pathway. Meanwhile, the in-vivo effect was studied in an A549 xenograft mouse model. Oral administration of W934 inhibited the tumor growth in a dose-dependent manner. Hereby, W934 might be considered as a potential therapeutic drug candidate for non-small-cell lung cancer treatment.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research