Docosahexaenoic Acid Induces Cell Death in Human Non-Small Cell Lung Cancer Cells by Repressing mTOR via AMPK Activation and PI3K/Akt Inhibition

摘要: The anticancer properties and mechanism of action omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been demonstrated in several cancers; however, the lung cancer remains unclear. Here, we show that docosahexaenoic acid (DHA), a ω3-PUFA, induced apoptosis autophagy non-small cell (NSCLC) cells. DHA-induced death was accompanied by AMP-activated protein kinase (AMPK) activation inactivated phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target rapamycin (mTOR) signaling. Knocking down AMPK overexpressing Akt increased mTOR activity attenuated death, suggesting DHA induces via AMPK- Akt-regulated inactivation. This confirmed Fat-1 transgenic mice, which produce ω3-PUFAs. Lewis (LLC) tumor cells implanted into mice showed slower growth, lower phospho-Akt levels, higher levels than wild-type mice. Taken together, these data suggest NSCLC are associated with PI3K/Akt inhibition, turn lead to suppression mTOR; thus ω3-PUFAs may be utilized as potential therapeutic agents for treatment.