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桑色素通过信号转导和转录激活因子3抑制尿激酶型纤溶酶原激活剂,从而抑制骨肉瘤的迁移和侵袭。

Morin inhibits osteosarcoma migration and invasion by suppressing urokinase plasminogen activator through a signal transducer and an activator of transcription 3.

作者信息

Yang Jia-Sin, Chou Chia-Hsuan, Hsieh Yi-Hsien, Lu Peace Wun-Ang, Lin Ya-Chiu, Yang Shun-Fa, Lu Ko-Hsiu

机构信息

Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

Environ Toxicol. 2024 Apr;39(4):2024-2031. doi: 10.1002/tox.24100. Epub 2023 Dec 13.

Abstract

Osteosarcoma, the most common primary bone cancer that affects adolescents worldwide, has the early metastatic potential to be responsible for high mortality rates. Morin has a multipurpose role in numerous cancers, whereas little is known about its role in osteosarcoma migration and invasion. Therefore, we hypothesized that morin suppresses the invasive activities and the migratory potential of human osteosarcoma cells. Our results showed that morin reduced migration and invasion capabilities in human osteosarcoma U2OS and HOS cells. Moreover, morin inhibited the urokinase plasminogen activator (uPA) expression through a signal transducer and an activator of transcription-3 (STAT3) phosphorylation. After STAT3 overexpression, the decrease of the migratory potential and uPA expression caused by 100 μM of morin in U2OS cells was countered, indicating that STAT3 contributes to the antimetastatic property of morin in human osteosarcoma cells by reducing uPA. In conclusion, morin may be a potential candidate for the antimetastatic treatment of human osteosarcoma.

摘要

骨肉瘤是全球影响青少年的最常见原发性骨癌,具有早期转移潜能,导致高死亡率。桑色素在多种癌症中具有多种作用,而其在骨肉瘤迁移和侵袭中的作用却鲜为人知。因此,我们推测桑色素可抑制人骨肉瘤细胞的侵袭活性和迁移潜能。我们的结果表明,桑色素降低了人骨肉瘤U2OS和HOS细胞的迁移和侵袭能力。此外,桑色素通过信号转导子和转录激活子3(STAT3)磷酸化抑制尿激酶型纤溶酶原激活剂(uPA)的表达。STAT3过表达后,100μM桑色素引起的U2OS细胞迁移潜能和uPA表达的降低得到了逆转,这表明STAT3通过降低uPA促进了桑色素在人骨肉瘤细胞中的抗转移特性。总之,桑色素可能是人类骨肉瘤抗转移治疗的潜在候选药物。

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