Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti‐tumor, anti‐inflammatory, and anti‐oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non‐toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down‐regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA‐induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti‐invasive effect of AA on osteosarcoma cells via the p‐AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

中文翻译：

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积雪草酸通过 AKT/Sp1/MMP1 轴抑制骨肉瘤细胞迁移和侵袭

骨肉瘤是一种影响青少年和儿童的恶性骨肿瘤。目前尚无有效的治疗方法。积雪草酸 (AA)，一种三萜类化合物，存在于积雪草，对各种类型的肿瘤细胞具有抗肿瘤、抗炎和抗氧化特性。本研究旨在确定 AA 是否对人骨肉瘤细胞发挥抗肿瘤作用。我们的结果表明，AA 在无毒条件下不影响人骨肉瘤细胞的活力、增殖率或细胞周期阶段。 AA 通过下调基质金属蛋白酶 1 (MMP1) 表达来抑制骨肉瘤细胞迁移和侵袭。 TNMplot 数据库中的数据表明，骨肉瘤中 MMP1 的表达高于正常组织，在骨肉瘤患者中观察到相关的临床意义。骨肉瘤细胞中 MMP1 的过度表达逆转了 AA 诱导的细胞迁移和侵袭抑制。 AA处理降低了特异性蛋白1（Sp1）的表达，而Sp1过表达消除了AA对MMP1表达以及细胞迁移和侵袭的影响。 AA 抑制 AKT 磷酸化，PI3K 抑制剂（渥曼青霉素）治疗可增强 AA 通过 p-AKT/Sp1/MMP1 轴对骨肉瘤细胞的抗侵袭作用。因此，AA具有作为抗人骨肉瘤的抗癌药物的潜力。