骨肉瘤（OS）是骨骼组织中最常见的原发性恶性肿瘤，临床治疗中缺乏有效的治疗方法。传统中药（TCM）已经使用数千年，为OS管理提供了重要见解。没食子酸（GA）是一种天然的酚酸，富含于各种食品和草药中。GA的多种药理活性，如抗氧化和抗炎，已被广泛认可。然而，其在OS中的生物学功能仍未完全理解。本研究评估了GA在143B、U2OS和MG63细胞中的潜在抗癌特性。研究了其对这些OS细胞的细胞生长、细胞周期、凋亡和迁移的影响。通过qPCR、荧光素酶活性和Western blotting检测，检测了长链非编码RNA（lncRNA）H19和Wnt/β-连环蛋白信号。采用原位小鼠模型研究了GA对肿瘤生长的影响。本研究发现，GA通过诱导OS细胞的细胞周期阻滞和凋亡，抑制了体外肿瘤生长，并抑制了侵袭和转移。使用原位小鼠模型，GA也被发现能够抑制体内肿瘤生成。GA被证明可以下调lncRNA H19，并破坏OS细胞中的经典Wnt/β-连环蛋白信号。此外，H19的异位表达可以挽救GA对肿瘤生长和转移的抑制作用，并在一定程度上逆转了Wnt/β-连环蛋白信号的失活。综上所述，我们的研究结果表明，GA通过H19介导Wnt/β-连环蛋白信号调控轴在OS细胞中抑制肿瘤生长。本研究所获得的信息提供了GA介导的抗OS活性的新机制，表明GA可能是OS患者的一种有前途的药物候选物。© 2022 The Authors.

Osteosarcoma (OS) is the most common primary malignancy in bone tissues, and effective therapeutics remain absent in clinical practice. Traditional Chinese medicines (TCM) have been used for thousands of years, which provide great insights into OS management. Gallic acid (GA) is a natural phenolic acid enriched in various foods and herbs. Several pharmacological activities of GA such as anti-oxidation and anti-inflammation have been well-established. However, its biological function in OS remains not fully understood.The potential anti-cancer properties of GA were evaluated in 143 ​B, U2OS and MG63 ​cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these OS cells. The lncRNA H19 and Wnt/β-catenin signaling were detected by qPCR, luciferase activity and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using an orthotopic mouse model.In the present study, GA was found to suppress the tumor growth in vitro via inducing cell cycle arrest and apoptosis in OS cells, and inhibit the invasion and metastasis as well. Using the orthotopic animal model, GA was also found to suppress tumorigenesis in vivo. Long noncoding RNA (lncRNA) H19 was demonstrated to be down-regulated by GA, and thus disrupted the canonical Wnt/β-catenin signaling in OS cells. Furthermore, the ectopic expression of H19 rescued the GA-induced suppressive effects on tumor growth and metastasis, and partially reversed the inactivation of Wnt/β-catenin signaling.Taken together, our results indicated that GA inhibited tumor growth through an H19-mediated Wnt/β-catenin signaling regulatory axis in OS cells.The information gained from this study provides a novel underlying mechanism of GA mediated anti-OS activity, suggesting that GA may be a promising drug candidate for OS patients.© 2022 The Authors.