自噬
癌症研究
ATG5型
细胞毒性
细胞生物学
下调和上调
青蒿琥酯
化学
程序性细胞死亡
生物
细胞凋亡
免疫学
生物化学
体外
恶性疟原虫
疟疾
基因
作者
Jie Zhang,Long Zhou,Jianbin Xiang,Chunsheng Jin,Ming‐Qing Li,Yongzhong He
标识
DOI:10.1016/j.intimp.2021.107705
摘要
Uterine corpus endometrial carcinoma (UCEC) is the most prevalent gynecologic cancer in developed countries and lacks efficient therapeutic strategies. Artesunate (ART), a well-modified derivate of artemisinin, exerts potent anti-cancer effects apart from its classical anti-malaria feature. Autophagy is a universal double-edged process in cell survival, and CD155 is a novel immune checkpoint highly expressed in numerous cancers. However, the relationships among ART, autophagy, and CD155 remain unclear in UCEC. In this study, we discovered that ART not only inhibited proliferation and migration, promoted apoptosis, but also induced autophagy in UCEC cells. Meanwhile, ART-induced autophagy elevated the level of CD155 in UCEC cells, thereby enhancing the cytotoxicity of natural killer cell line (NK92) by modulating the interactions between CD155 and its receptors in NK92 cells via upregulation of co-stimulator CD226 and downregulation of co-inhibitor TIGIT. Additionally, ART regulated CD155 partially via ATG5, and knockdown of ATG5 dampened the expression of CD155 in UCEC cells, thus decreasing the cytotoxicity of NK92 cells. Therefore, this study demonstrated the dual anti-cancer effects of ART as it could induce cell-killing directly and indirectly, which provides novel insights into the anti-cancer mechanisms of ART on UCEC.
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