Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the human brain and works as an anticancer agent to induce cell cycle arrest and apoptosis in glioblastoma multiforme (GBM) cell lines. However, little is known about the connection between DHA and autophagy in GBM cells. We found that high-dose DHA caused cellular autophagy in cultured U251 and U118 GBM cell lines, but there was no effect with a low dose. Moreover, after treatment with a high dose of DHA at 12, 24, and 48 h, the protein expression of SQSTM1/p62 decreased in DHA-treated U251 cells at 12 and 24 h, but increased at 48 h, while in DHA-treated U118 cells, the protein expression increased at all time points. Interestingly, the level of SQSTM1/p62 mRNA was elevated in both DHA-treated U251 and U118 cells at all time points, indicating that DHA activated SQSTM1/p62 transcription in both cell lines. Furthermore, downregulation of SQSTM1/p62 by siRNA attenuated DHA-induced cellular autophagy in both cell lines. This report confirms that high-dose DHA induces cellular autophagy in GBM cells, and demonstrates that SQSTM1/p62 acts as a regulator and participates in DHA-induced autophagy.

中文翻译：

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SQSTM1 / p62参与二十二碳六烯酸诱导的胶质母细胞瘤细胞系细胞自噬。

二十二碳六烯酸（DHA）是人脑中最丰富的n-3多不饱和脂肪酸，可作为抗癌剂来诱导胶质母细胞瘤（GBM）细胞系中的细胞周期停滞和凋亡。但是，关于GBM细胞中DHA与自噬之间的联系知之甚少。我们发现大剂量DHA在培养的U251和U118 GBM细胞系中引起细胞自噬，但低剂量无作用。此外，在第12、24和48小时用高剂量的DHA处理后，SQSTM1 / p62的蛋白质表达在DHA处理的U251细胞中在12和24小时减少，但在48 h时增加，而在DHA处理的时候在U118细胞中，蛋白质表达在所有时间点均增加。有趣的是，在所有时间点，DHA处理的U251和U118细胞中SQSTM1 / p62 mRNA的水平均升高，表明DHA激活了两种细胞系中的SQSTM1 / p62转录。此外，siRNA对SQSTM1 / p62的下调减弱了两种细胞系中DHA诱导的细胞自噬。该报告证实高剂量DHA诱导GBM细胞中的细胞自噬，并证明SQSTM1 / p62充当调节剂并参与DHA诱导的自噬。