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芒柄花苷通过限制MMP2/9和EGFR-Erk1/2信号通路对人骨肉瘤细胞的抗侵袭和抗迁移作用

Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway.

作者信息

Gong Guowei, Ganesan Kumar, Xiong Qingping, Zheng Yuzhong

机构信息

Department of Bioengineering, Zunyi Medical University, Zhuhai Campus, Zhuhai 519041, China.

Guangdong Key Laboratory for Functional Substances in Medicinal Edible Resources and Healthcare Products, School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, China.

出版信息

Cancers (Basel). 2023 Jan 26;15(3):758. doi: 10.3390/cancers15030758.

DOI:10.3390/cancers15030758
PMID:36765716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913877/
Abstract

Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes the leading cause of cancer death worldwide. Ononin is an isoflavone glycoside known to have various pharmacological properties, including antioxidant and anti-inflammatory activities. In the present study, we aimed to investigate the efficacy of ononin on osteosarcoma cell migration, invasion, and the underlying mechanisms. The in vitro anti-tumorigenic and anti-migratory properties of ononin were determined by MTT, colony formation, invasion, and migration in MG-63 and U2OS osteosarcoma cell lines. The results were compared with the standard chemotherapeutic drug, doxorubicin (DOX), as a positive control. The dose-dependent manners of ononin treatment increased the expression of apoptosis and inhibition of cell proliferation through the EGFR-Erk1/2 signaling pathways. Additionally, ononin significantly inhibited the invasion and migration of human osteosarcoma cells. For consistency, we used the MG-63-xenograft mice model to confirm the in vivo anti-tumorigenic and anti-migratory efficacy of ononin by inhibiting the protein expressions of EGFR-Erk1/2 and MMP2/9. According to the histological study, ononin had no adverse effect on the liver and kidney. Overall, our findings suggested that ononin could be a potentially effective agent against the development and metastasis of osteosarcoma.

摘要

骨肉瘤是一种常见的骨恶性肿瘤。由于其高转移特性,骨肉瘤成为全球癌症死亡的主要原因。芒柄花素是一种异黄酮苷,已知具有多种药理特性,包括抗氧化和抗炎活性。在本研究中,我们旨在研究芒柄花素对骨肉瘤细胞迁移、侵袭的疗效及其潜在机制。通过MTT法、集落形成实验、侵袭实验和迁移实验,在MG-63和U2OS骨肉瘤细胞系中测定了芒柄花素的体外抗肿瘤和抗迁移特性。将结果与标准化疗药物阿霉素(DOX)作为阳性对照进行比较。芒柄花素治疗的剂量依赖性方式通过EGFR-Erk1/2信号通路增加了细胞凋亡的表达并抑制了细胞增殖。此外,芒柄花素显著抑制了人骨肉瘤细胞的侵袭和迁移。为了保持一致性,我们使用MG-63异种移植小鼠模型,通过抑制EGFR-Erk1/2和MMP2/9的蛋白表达来证实芒柄花素在体内的抗肿瘤和抗迁移疗效。根据组织学研究,芒柄花素对肝脏和肾脏没有不良影响。总体而言,我们的研究结果表明芒柄花素可能是一种对抗骨肉瘤发展和转移的潜在有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f98/9913877/908a8897a164/cancers-15-00758-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f98/9913877/9c157ddddfa9/cancers-15-00758-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f98/9913877/3e32b079c900/cancers-15-00758-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f98/9913877/761d1b87a7d2/cancers-15-00758-g007.jpg
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