Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells.
Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells.
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DOI：
10.3892/ol.2015.3110
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发表时间：
2015-06
期刊：
影响因子：
2.9
通讯作者：
Qinghua Yao;T. Fu;Lu Wang;Yuebiao Lai;Yuqi Wang;Chao Xu;Lulu Huang;Yong Guo
中科院分区：
文献类型：
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作者：
Qinghua Yao;T. Fu;Lu Wang;Yuebiao Lai;Yuqi Wang;Chao Xu;Lulu Huang;Yong Guo
本研究发现ω-3长链多不饱和脂肪酸（ω-3 PUFAs）、二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）对肺癌A549细胞具有抗增殖作用。进行MTS和细胞毒性测定以证实ω-3 PUFA诱导细胞死亡。同时检测了自噬相关基因和信号通路。发现用DHA和EPA处理后微管相关蛋白轻链3（LC 3）表达增加，并且LC 3-II的表达特别增加。mRFP-GFP-LC 3荧光染色和p62表达水平检测自噬通量。目前的结果表明，DHA和EPA阻断自噬通量，表明自噬体积累。在用干扰自噬体的DHA和EPA处理后，Beclin 1的表达显著降低，而磷酸化Akt和磷酸化哺乳动物雷帕霉素靶蛋白的表达显著增加。因此，DHA和EPA通过抑制A549细胞中的自噬而发挥抗增殖作用，这突出了DHA和EPA用于预防或治疗肺癌的潜力。
The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and EPA, and the expression of LC3-II was particularly increased. mRFP-GFP-LC3 fluorescence staining and p62 expression levels were used to detect autophagic flux. The present results indicate that DHA and EPA block autophagic flux, suggesting autophagosome accumulation. Subsequent to treatment with DHA and EPA, which interfered with autophagosomes, the expression of Beclin 1 was significantly decreased, while the expression of phosphorylated Akt and phosphorylated mammalian target of rapamycin was significantly increased. Therefore, DHA and EPA exert anti-proliferative effects by inhibiting autophagy in A549 cells, which highlights the potential of DHA and EPA for use in the prevention or treatment of lung cancer.