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乌索酸通过抑制丝裂原活化蛋白激酶和基质金属蛋白酶来抑制人骨肉瘤细胞的迁移和侵袭。

Ursonic acid inhibits migration and invasion of human osteosarcoma cells through the suppression of mitogen-activated protein kinases and matrix metalloproteinases.

作者信息

Son Juhyeon, Cha Hansol, Lee Sungeun, Bae Yongwoong, Ryou Chongsuk, Lee Sang Yeol

机构信息

Department of Life Sciences, College of BioNano Technology, Gachon University, Seongnam, 13120, Gyeonggi, Korea.

Department of Pharmacy and Institute of Pharmaceutical Sciences and Technology, Hanyang University, Ansan, Gyeonggi, Korea.

出版信息

Mol Biol Rep. 2023 May;50(5):4029-4038. doi: 10.1007/s11033-023-08333-4. Epub 2023 Feb 27.

Abstract

INTRODUCTION

Osteosarcoma (OS) is the most common form of bone malignancy. Although contemporary chemotherapy and surgery have improved the prognosis of those with OS, developing new OS therapies has proven difficult for some time. The activation of the matrix metalloproteinase (MMP) and mitogen-activated protein kinase (MAPK) signaling pathways can induce metastasis, which is an obstacle to OS treatment. Ursonic acid (UNA) is a phytochemical with the potential to cure a variety of human ailments, including cancer.

METHODS AND RESULTS

In this study, we investigated the anti-tumor properties of UNA in MG63 cells. We conducted colony formation assay, wound healing assay, and Boyden chamber assays to investigate the anti-OS effects of UNA. UNA was found to significantly inhibit the proliferative, migratory, and invasive abilities of MG63 cells. This bioactivity of UNA was mediated by the inhibition of extracellular signal-regulated kinase (ERK) and p38 and reduction of MMP-2 transcriptional expression as observed in western blot analysis, gelatin zymography and RT-PCR. Anti-OS activities of UNA were also observed in Saos2 and U2OS cells, indicating that its anti-cancer properties are not specific to cell types.

CONCLUSION

Our findings suggest that UNA has the potential for use in anti-metastatic drugs in the treatment of OS.

摘要

引言

骨肉瘤(OS)是最常见的骨恶性肿瘤形式。尽管当代化疗和手术改善了骨肉瘤患者的预后,但一段时间以来,开发新的骨肉瘤治疗方法已被证明具有难度。基质金属蛋白酶(MMP)和丝裂原活化蛋白激酶(MAPK)信号通路的激活可诱导转移,这是骨肉瘤治疗的一个障碍。乌索酸(UNA)是一种植物化学物质,具有治疗包括癌症在内的多种人类疾病的潜力。

方法与结果

在本研究中,我们研究了乌索酸在MG63细胞中的抗肿瘤特性。我们进行了集落形成试验、伤口愈合试验和博伊登小室试验,以研究乌索酸的抗骨肉瘤作用。发现乌索酸可显著抑制MG63细胞的增殖、迁移和侵袭能力。如在蛋白质免疫印迹分析、明胶酶谱分析和逆转录-聚合酶链反应中所观察到的,乌索酸的这种生物活性是通过抑制细胞外信号调节激酶(ERK)和p38以及降低MMP-2转录表达来介导的。在Saos2和U2OS细胞中也观察到了乌索酸的抗骨肉瘤活性,表明其抗癌特性并非细胞类型特异性的。

结论

我们的研究结果表明,乌索酸有潜力用于骨肉瘤治疗中的抗转移药物。

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