Abstract:
Allicin, an organic sulfur compound extracted from the bulb of Allium sativum, can potentially prevent various tumors. Our previous study found that allicin can effectively suppress the proliferation of osteosarcoma cells. However, the molecular mechanisms have not been illustrated. In this study, Saos-2 and U2OS osteosarcoma cells were used to investigate the underlying mechanisms. A series of experiments were carried out to authenticate the anticancer property of allicin. Knockdown of lncRNA MALAT1 inhibited the proliferation, invasion and migration and promoted apoptosis of osteosarcoma cells. Knockdown of miR-376a increased the proliferation, invasion, and migration and dropped apoptosis of osteosarcoma cells. Furthermore, knockdown of miR-376a reversed the influences of MALAT1 silencing in osteosarcoma cells. Based on our data, MALAT1 could downregulate the expression of miR-376a, subsequently accelerating osteosarcoma. Moreover, oxidative stress and autophagy were identified as the potential key pathway of allicin. Allicin inhibited osteosarcoma growth and promoted oxidative stress and autophagy via MALATI-miR-376a. We also found that allicin promotes oxidative stress and autophagy to inhibit osteosarcoma growth by inhibiting the Wnt/β-catenin pathway in vivo and in vitro. All data showed that allicin promotes oxidative stress and autophagy of osteosarcoma via the MALATI-miR-376a-Wnt/β-catenin pathway.
摘要:
大蒜素,从葱属鳞茎中提取的一种有机硫化合物,可以预防各种肿瘤。我们先前的研究发现大蒜素可以有效抑制骨肉瘤细胞的增殖。然而,分子机制尚未阐明。在这项研究中,Saos-2和U2OS骨肉瘤细胞用于研究潜在的机制。进行了一系列实验以验证大蒜素的抗癌性质。敲除lncRNAMALAT1抑制增殖,骨肉瘤细胞的侵袭和迁移并促进其凋亡。miR-376a的敲减增加了增殖,入侵,骨肉瘤细胞的迁移和凋亡下降。此外,miR-376a敲低可逆转骨肉瘤细胞MALAT1沉默的影响.根据我们的数据,MALAT1可以下调miR-376a的表达,随后加速骨肉瘤。此外,氧化应激和自噬是大蒜素潜在的关键通路。大蒜素通过MALATI-miR-376a抑制骨肉瘤生长并促进氧化应激和自噬。我们还发现大蒜素在体内和体外通过抑制Wnt/β-catenin通路促进氧化应激和自噬来抑制骨肉瘤的生长。所有数据显示大蒜素通过MALATI-miR-376a-Wnt/β-catenin途径促进骨肉瘤的氧化应激和自噬。