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通过抑制 Wnt/β-连环蛋白信号通路对人骨肉瘤细胞发挥抗癌作用。

Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway.

机构信息

The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China.

The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, Guangdong, People's Republic of China.

出版信息

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419890917. doi: 10.1177/1534735419890917.

Abstract

Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. , a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. To investigate the effect of on osteosarcoma cells and its mechanism. Osteosarcoma MG63 and U2-OS cells were treated with , followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Our results suggest that broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.

摘要

目前,骨肉瘤的治疗在一定程度上受到副作用和低耐受性的限制,而这些问题通常可以通过中药来避免。 是一种具有抗肿瘤作用的中药,为骨肉瘤提供了一种潜在的替代方法,但对其在骨肉瘤细胞中的分子机制知之甚少。 为了研究 对骨肉瘤细胞的作用及其机制。 用 处理骨肉瘤 MG63 和 U2-OS 细胞,然后进行细胞增殖(细胞计数试剂盒-8)、集落形成和凋亡(Alexa Fluor 647-Annexin V/碘化丙啶,流式细胞术)检测。通过划痕愈合和 Transwell 侵袭实验评估细胞的迁移和侵袭,通过实时定量聚合酶链反应、western blot 和双荧光素酶实验研究 对 Wnt/β-catenin 信号转导的影响。 抑制人骨肉瘤 MG63 和 U2-OS 细胞的增殖、迁移和侵袭,并诱导细胞凋亡。双荧光素酶实验表明, 抑制了 Wnt/β-catenin 信号通路中转录因子/淋巴细胞增强因子的转录活性。此外, 通过抑制 Wnt 共受体 LRP5 和 Wnt 相关靶基因,如 β-catenin、cyclin D1、C-Myc、MMP-2 和 MMP-9,阻断了 Wnt/β-catenin 信号通路。同时,当 Wnt/β-catenin 被抑制时,E-钙黏蛋白的表达上调。 我们的研究结果表明, 通过抑制 Wnt/β-catenin 信号通路,广泛抑制骨肉瘤细胞生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2428/6923688/184e17310c7f/10.1177_1534735419890917-fig1.jpg

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