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

作者：Kim, Nayeong; Jeong, Soyeon; Jing, Kaipeng; Shin, Soyeon; Kim, Soyeon; Heo, Jun-Young; Kweon, Gi-Ryang; Park, Seung-Kiel; Wu, Tong; Park, Jong-Il; Lim, Kyu^*

来源：Biomed Research International, 2015, 2015: 239764.

DOI：10.1155/2015/239764

• INDUCED APOPTOSIS
• PROTEIN-KINASES
• AUTOPHAGY
• RAPAMYCIN
• SURVIVAL
• STRESS
• TARGET
• LINE

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

• 出版日期2015
• 单位广东医科大学