Artesunate-induced ATG5-related autophagy enhances the cytotoxicity of NK92 cells on endometrial cancer cells via interactions between CD155 and CD226/TIGIT
| Autor: | Long Zhou, Chun-Sheng Jin, Jie Zhang, Ming-Qing Li, Jiangdong Xiang, He Yinyan |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
CD226 Immunology ATG5 Artesunate Down-Regulation Autophagy-Related Protein 5 Natural killer cell 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation TIGIT Cell Line Tumor Autophagy medicine Humans Immunology and Allergy Receptors Immunologic Cytotoxicity Pharmacology Chemistry Coculture Techniques Immune checkpoint Endometrial Neoplasms Gene Expression Regulation Neoplastic Killer Cells Natural 030104 developmental biology medicine.anatomical_structure Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research Receptors Virus Female Drug Screening Assays Antitumor Signal Transduction |
| Zdroj: | International Immunopharmacology. 97:107705 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2021.107705 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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