CLG promotes mTOR/ULK1 pathway-mediated autophagy to inhibit OS development by inhibiting TRAF6-mediated FLT3 ubiquitination

IF 4.5 2区医学 Q1 ONCOLOGY Cancer Science Pub Date : 2024-08-09 DOI:10.1111/cas.16274

Xiongjie Huang, Yanran Huang, Bin Peng, Junfang Wang, Huiyu Tang, Yanming Chen

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Abstract

Corilagin (CLG) has antitumor activities in certain human malignant cancers. Herein, the effects and mechanisms of CLG on osteosarcoma (OS) were investigated. OS cell viability and proliferation were detected by MTT and colony formation assay. Cell cycle and apoptosis were examined using flow cytometry. The interaction between TRAF6 and FLT3 was investigated using a co-immunoprecipitation assay. Results demonstrated that CLG treatment inhibited OS cell viability and proliferation but promoted OS cell autophagy and apoptosis in a concentration-dependent manner. Mechanically, CLG inhibited TRAF6-mediated FLT3 ubiquitination degradation. TRAF6 overexpression abolished the effects of CLG on OS cell proliferation, autophagy, and apoptosis. Finally, CLG administration inhibited OS tumor growth in mice by inducing autophagy-dependent apoptosis. Taken together, CLG inhibited OS progression by facilitating mTOR/ULK1 pathway-mediated autophagy through inhibiting TRAF6-mediated FLT3 ubiquitination, which indicated that CLG was a promising candidate for the treatment of OS.

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CLG通过抑制TRAF6介导的FLT3泛素化，促进mTOR/ULK1通路介导的自噬，从而抑制OS的发展。

柯里拉京（CLG）对某些人类恶性癌症具有抗肿瘤活性。本文研究了CLG对骨肉瘤（OS）的作用和机制。通过 MTT 和集落形成试验检测了骨肉瘤细胞的活力和增殖。流式细胞术检测了细胞周期和细胞凋亡。使用共免疫共沉淀试验研究了 TRAF6 和 FLT3 之间的相互作用。结果表明，CLG以浓度依赖的方式抑制了OS细胞的活力和增殖，但促进了OS细胞的自噬和凋亡。CLG从机制上抑制了TRAF6介导的FLT3泛素化降解。TRAF6过表达可消除CLG对OS细胞增殖、自噬和凋亡的影响。最后，CLG通过诱导自噬依赖性凋亡抑制了小鼠OS肿瘤的生长。综上所述，CLG通过抑制TRAF6介导的FLT3泛素化来促进mTOR/ULK1通路介导的自噬，从而抑制了OS的进展，这表明CLG是一种治疗OS的有希望的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Science 医学-肿瘤学

自引率

3.50%

发文量

406

审稿时长

2 months

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.

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