Wen Jian, Chen Hanren, Ren Zhongyu, Zhang Peng, Chen Jianjiao, Jiang Shulian
Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guilin Medical 26, University, 15 Lequn road, Guilin, 541000, People's Republic of China.
Nanjing Second Hospital, 1 Zhongfu road, Nanjing, 210003, People's Republic of China.
Nano Converg. 2021 Apr 2;8(1):10. doi: 10.1186/s40580-021-00260-z.
Iron-based nanoparticles, which could elicit ferroptosis, is becoming a promising new way to inhibit tumor cell growth. Notably, ultrasmall iron oxide nanoparticles (USIONPs) have been found to upregulate the autophagy process in glioblastoma (GBM) cells. Whether USIONPs could also elicit ferroptosis and the relationship between the USIONPs-induced autophagy and ferroptosis need to be explored. In the current study, our synthesized USIONPs with good water solubility could significantly upregulate the ferroptosis markers in GBM cells, and downregulate the expression of anti-ferroptosis genes. Interestingly,ferrostatin-1 could reverse USIONPs- induced ferroptosis, but inhibitors of apoptosis, pyroptosis, or necrosis could not. Meanwhile, autophagy inhibitor 3-methyladenine could also reverse the USIONPs-induced ferroptosis. In addition, shRNA silencing of upstream genes Beclin1/ATG5 of autophagy process could significantly reverse USIONPs-induced ferroptosis, whereas overexpression of Beclin1/ATG5 of autophagy process could remarkably promote USIONPs-induced ferroptosis. Furthermore, lysosome inhibitors could significantly reverse the USIONPs-induced ferroptosis. Collectively, these facts suggest that USIONPs-induced ferroptosis is regulated via Beclin1/ATG5-dependent autophagy pathway.
能够引发铁死亡的铁基纳米颗粒正成为一种抑制肿瘤细胞生长的有前景的新方法。值得注意的是，已发现超小氧化铁纳米颗粒（USIONPs）可上调胶质母细胞瘤（GBM）细胞中的自噬过程。USIONPs是否也能引发铁死亡以及USIONPs诱导的自噬与铁死亡之间的关系有待探索。在当前研究中，我们合成的具有良好水溶性的USIONPs可显著上调GBM细胞中的铁死亡标志物，并下调抗铁死亡基因的表达。有趣的是，铁死亡抑制剂1可逆转USIONPs诱导的铁死亡，但凋亡、焦亡或坏死的抑制剂则不能。同时，自噬抑制剂3-甲基腺嘌呤也可逆转USIONPs诱导的铁死亡。此外，对自噬过程的上游基因Beclin1/ATG5进行shRNA沉默可显著逆转USIONPs诱导的铁死亡，而自噬过程中Beclin1/ATG5的过表达可显著促进USIONPs诱导的铁死亡。此外，溶酶体抑制剂可显著逆转USIONPs诱导的铁死亡。总的来说，这些事实表明USIONPs诱导的铁死亡是通过Beclin1/ATG5依赖性自噬途径调节的。
