雷公藤醇
癌症研究
细胞凋亡
神经生长因子IB
自噬
结直肠癌
癌细胞
细胞生长
化学
癌症
医学
内科学
生物化学
转录因子
核受体
基因
作者
Wenxin Zhang,Zimei Wu,Qi Hu,Lu Chen,Tianxiao Wang,Xiang Mao,Hui Shi,Haifei Chen,Ming Zhong,Xiaojin Shi,Xinhai Wang,Qunyi Li
出处
期刊:Phytomedicine
[Elsevier]
日期:2022-09-01
卷期号:104: 154280-154280
被引量:12
标识
DOI:10.1016/j.phymed.2022.154280
摘要
Celastrol is a biologically active ingredient extracted from Tripterygium wilfordii that has exerted properties of anti-cancer. We explored the anti-tumor activities of celastrol against colorectal cancer (CRC) and the potential signaling pathways involved in its mechanism in this study. The main purpose was to investigate the anti-CRC effects of celastrol and its novel potential mechanisms. HCT-116 and SW480 cell lines were used for in vitro studies, the mouse xenograft model of CRC tumor was performed for in vivo studies. The effects of celastrol on colorectal cancer cells in vitro and underlying mechanisms were examined by using western blot analysis, cell proliferation assays, PI and Annexin-V staining assays, immunofluorescence and qRT-PCR assay. CRC xenografts model and IHC-staining were mainly used to evaluate the effects of celastrol in vivo. The results demonstrated that celastrol induced apoptosis and inhibited proliferation in CRC cells. The expression of Nur77 influenced the anti-CRC effects of celastrol, and inhibitory effect of celastrol on CRC cells could be reversed by overexpressing Nur77. Celastrol induced autophagy and the autophagy inhibition enhanced the anti-CRC effects. The ATG7 was up-regulated obviously after celastrol treatment for Nur77 overexpressing CRC cancer cells. Treating mice implanted with CRC cells with celastrol showed that it effectively inhibited tumor growth, which was associated with the down-regulation of Nur77. Levels of Nur77 and ATG7 were correlated with survival in human colorectal cancer. Celastrol induced apoptosis and autophagy played an important role in human colorectal cancer, Nur77 was involved in the anti-CRC effect of celastrol and decreased expression of Nur77 induced high expression of ATG7. Celastrol exerted anti-CRC effects by inhibiting Nur77 to induce high expression of ATG7 signaling and Nur77/ATG7 signaling may be a potential pathway for colorectal cancer treatment.
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