Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; Department of Immunology and Microbiology, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
Department of Immunology and Microbiology, Shanghai Institute of Immunology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
Biomed Pharmacother. 2020 May;125:109984. doi: 10.1016/j.biopha.2020.109984. Epub 2020 Feb 25.
Melanoma is a life-threatening cancer with limited treatments. Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) crucial to RNA virus sensing, interferon production, and tumor suppression. Quercetin, a natural flavonoid, has particularly therapeutic interests to prevent and treat cancer, for its pharmacological effects against oxidant, inflammation, and angiogenesis. Quercetin was investigated for its anti-melanoma activity and potential mechanisms in this study. We found that quercetin inhibited mouse melanoma growth in vivo, and suppressed proliferation and promoted apoptosis of both B16 and A375 cells in vitro. Quercetin upregulated IFN-α and IFN-β expression through activating RIG-I promoter in B16 cells. The induction of IFN-α and IFN-β, which could be severely impaired by silencing RIG-I induced interferon stimulated genes (ISGs). Moreover, RIG-I likely amplifies antitumor effects by activating signal transduction and activator of transcription 1 (STAT1) in the IFN-JAK-STAT pathway in an autocrine and paracrine manner. Our study provided novel insights regarding biological and anti-proliferative activities of quercetin against melanoma, and we identified RIG-I as a potential target in anti-tumor therapies.
黑色素瘤是一种危及生命的癌症，治疗方法有限。视黄酸诱导基因 I（RIG-I）是一种细胞溶质模式识别受体（PRR），对于 RNA 病毒的感应、干扰素的产生和肿瘤抑制至关重要。槲皮素是一种天然类黄酮，因其对氧化剂、炎症和血管生成的药理学作用而具有特别的治疗兴趣，可用于预防和治疗癌症。本研究旨在研究槲皮素的抗黑色素瘤活性及其潜在机制。我们发现，槲皮素在体内抑制小鼠黑色素瘤的生长，并在体外抑制 B16 和 A375 细胞的增殖，促进其凋亡。槲皮素通过激活 B16 细胞中的 RIG-I 启动子，上调 IFN-α 和 IFN-β 的表达。IFN-α 和 IFN-β 的诱导可被沉默 RIG-I 诱导的干扰素刺激基因（ISGs）严重破坏。此外，RIG-I 可能通过在 IFN-JAK-STAT 通路中以自分泌和旁分泌的方式激活信号转导和转录激活因子 1（STAT1）来放大抗肿瘤作用。我们的研究提供了关于槲皮素对黑色素瘤的生物学和抗增殖活性的新见解，并确定 RIG-I 是抗肿瘤治疗的潜在靶点。
