Dual inhibition of phosphatidylinositol 3-kinase/Akt and mammalian target of rapamycin signaling in human nonsmall cell lung cancer cells by a dietary flavonoid fisetin

摘要: Lung cancer is one of the most commonly occurring malignancies. It has been reported that mammalian target rapamycin (mTOR) phosphorylated in lung and its activation was more frequent tumors with overexpression phosphatidylinositol 3-kinase (PI3K)/Akt. Therefore, dual inhibitors PI3K/Akt mTOR signaling could be valuable agents for treating cancer. In present study, we show fisetin, a dietary tetrahydroxyflavone inhibits cell growth concomitant suppression human nonsmall (NSCLC) cells. Using autodock 4, found fisetin physically interacts complex at two sites. Fisetin treatment also to reduce formation A549 colonies dose-dependent manner. Treatment cells caused decrease protein expression PI3K (p85 p110), inhibition phosphorylation Akt, mTOR, p70S6K1, eIF-4E 4E-BP1. Fisetin-treated exhibited constituents such as Rictor, Raptor, GβL PRAS40. There an increase AMPKα TSC2 on fisetin. We inhibitor mTOR-siRNA proteins which were further downregulated suggesting these effects are mediated part, through signaling. Our results suppressed NSCLC thus, developed chemotherapeutic agent against