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Tizoxanide induces autophagy by inhibiting PI3K/Akt/ mTOR pathway in RAW264.7 macrophage cells
Jiaoqin Shou,Mi Wang,Xiaolei Cheng,Xiaoyang Wang,Lifang Zhang,Yingchun Liu,Chenzhong Fei,Chunmei Wang,Feng Gu,Feiqun Xue,Juan Li,Keyu Zhang 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.2
As the main metabolite of nitazoxanide, tizoxanide(TIZ) has a broad-spectrum anti-infective effect againstparasites, bacteria, and virus. In this study, we investigatedthe effects of TIZ on autophagy by regulating the PI3K/Akt/mTOR signaling pathway. RAW264.7 macrophage cellswere treated with various TIZ concentrations. Cell viabilityassay, transmission electron microscope, and immunofluorescencestaining were used to detect the biological functionof the macrophage cells, and the expression levels of theautophagy pathway-related proteins were measured by Westernblot. Results revealed that TIZ promoted the conversionof LC3-I to LC3-II, the formation of autophagy vacuoles,and the degradation of SQSTM1/p62 in a concentration- andtime-dependent manner in RAW264.7 cells. Treatment withTIZ increased the Beclin-1 expression level and inhibitedPI3K, Akt, mTOR, and ULK1 activation. These effects wereenhanced by pretreatment with rapamycin but attenuated bypretreatment with LY294002. In addition, the conversion ofLC3-I to LC3-II was observed in Vero, 293T, and HepG2cells treated with TIZ. These data suggested that TIZ mayinduce autophagy by inhibiting the Akt/mTOR/ULK1 signalingpathway in macrophages and other cells.