Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc

Purpose: To determine the anti-proliferative potential of quinolinone against gastric cancer cells, and the underlying mechanism of action.Methods: Quinolinone-mediated proliferative changes were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while its effect on apoptosis was determined by flow cytometry. Transwell and wound healing assays were used for the determination of the effect of quinolinone on cell invasion and migration. The effect of quinolinone on protein expression levels were assayed with western blotting.Results: Quinolinone caused reduction in gastric cancer cell viability, but it had no effect on normal (GES-1) cells. Treatment with 8 μM quinolinone reduced the viability of SNU-5 and SGC-7901 cells to 32 and 27 %, respectively. Moreover, 8 μM quinolinone induced 67.90 and 71.54 % apoptosis in SNU-5 and SGC-7901 cells, respectively. Quinolinone significantly increased the population of cells in G1 phase, and suppressed migration potential (p < 0.05). Furthermore, in quinolinone-treated cells, the expression levels of p-PI3K, c-Myc and p-AKT were much lower than those in untreated cells (p < 0.05). Quinolinone also downregulated the expressions of MMP-2 and MMP-9, while it upregulated p21 expression in SNU-5 and SGC-7901 cells.Conclusion: Quinolinone suppresses the growth of SNU-5 and SGC-7901 gastric cancer cells via cell cycle arrest, induction of apoptosis and downregulation of the expressions of c-Myc and metalloproteinases. Thus, quinolinone may be developed as a potential drug candidate for the treatment of gastric cancer. Keywords: Gastric cancer, Apoptosis, Metalloproteinases, Phosphorylatio

The Effects of Breathing Behaviour on Crack Growth of a Vibrating Beam

The effects of breathing behaviour on the dynamic response and crack growth are studied through a cracked cantilever beam. The main goal is to reveal the coupling mechanism of dynamic response and crack growth by employing a plain single-degree-of-freedom (SDOF) lumped system with the breathing crack stiffness and friction damping. The friction damping loss factor is derived by using Coulomb friction model and energy principle. Natural frequency, dynamic stress, dynamic stress intensity factor (DSIF), and crack growth are analyzed by case studies in the end. Results indicate that not only does the stiffness oscillates during crack growth corresponding to the physically open and closed states of the crack, but also stiffness and friction damping oscillate nonlinearly with crack growth. This behaviour induces not only nonlinear dynamic response but also nonlinear crack growth. It provides an approximate description of the nonlinearities introduced by the presence of a breathing crack. Therefore, it can be employed to improve the prediction precision of the crack identification and crack growth life of a cracked cantilever beam