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姜黄素增强自噬相关蛋白3(ATG3)依赖性自噬并抑制宫颈癌转移。

Curcumin enhances ATG3-dependent autophagy and inhibits metastasis in cervical carcinoma.

作者信息

Zheng Fei, Lu Jingjing, Wang Chuhan, Yu Huimin, Fu Yanhong, Ma Danli

机构信息

Department of Gynecology, Ningbo No. 2 Hospital (Hwa Mei Hospital, University of Chinese Academy of Sciences), Ningbo, Zhejiang Province, 315000, China.

Department of Gynecology, Ningbo University Affiliated People's Hospital, Ningbo, Zhejiang Province, 315000, China.

出版信息

Cell Div. 2024 Nov 28;19(1):33. doi: 10.1186/s13008-024-00138-6.

Abstract

Cervical carcinoma poses a significant health threat, with traditional treatments proving inadequate in advanced stages. Curcumin, a bioactive compound derived from turmeric, exhibits notable anti-inflammatory, antioxidant, and antineoplastic properties, potentially modulating autophagy, and metastasis in cancer cells. This study examines curcumin's impact on autophagy and metastasis in cervical carcinoma, focusing on its interaction with autophagy-related gene 3 (ATG3). SiHa and HeLa cervical carcinoma cell lines were treated with curcumin, ATG3 knockdown (shATG3), and their combination. Cell migration was evaluated via wound healing assays, while cell proliferation was evaluated with CCK-8 assays. LC3 expression was assessed using immunofluorescence and western blotting. Molecular docking simulations identified curcumin's binding interactions with key proteins. Curcumin and shATG3 significantly inhibited both cell migration and proliferation, with a synergistic effect observed when combined. LC3 expression was enhanced, indicating increased autophagy. Docking studies revealed curcumin's potential binding to MMP2, MMP9, TGF-β, ATG3, LC3, and p62, suggesting modulation of these pathways. The combination of curcumin and ATG3 knockdown significantly inhibited cervical carcinoma cell migration and proliferation, while also enhancing autophagy, supporting the potential of curcumin as a therapeutic agent for cervical carcinoma. Further clinical research is needed to validate these findings.

摘要

宫颈癌对健康构成重大威胁,传统治疗方法在晚期已被证明效果不佳。姜黄素是一种从姜黄中提取的生物活性化合物,具有显著的抗炎、抗氧化和抗肿瘤特性,可能会调节癌细胞的自噬和转移。本研究考察姜黄素对宫颈癌自噬和转移的影响,重点关注其与自噬相关基因3(ATG3)的相互作用。用姜黄素、ATG3基因敲低(shATG3)及其组合处理SiHa和HeLa宫颈癌细胞系。通过伤口愈合试验评估细胞迁移,用CCK-8试验评估细胞增殖。使用免疫荧光和蛋白质印迹法评估LC3的表达。分子对接模拟确定了姜黄素与关键蛋白的结合相互作用。姜黄素和shATG3均显著抑制细胞迁移和增殖,联合使用时具有协同效应。LC3表达增强,表明自噬增加。对接研究显示姜黄素可能与基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、转化生长因子-β(TGF-β)、ATG3、LC3和p62结合,提示对这些途径有调节作用。姜黄素与ATG3基因敲低联合使用可显著抑制宫颈癌细胞迁移和增殖,同时增强自噬,这支持了姜黄素作为宫颈癌治疗药物的潜力。需要进一步的临床研究来验证这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a69/11606299/69a72fbe3ebd/13008_2024_138_Fig1_HTML.jpg

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