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萝卜硫素通过调控 FSTL1/NF-κB 通路抑制骨肉瘤的进展。

Sulforaphene inhibits the progression of osteosarcoma via regulating FSTL1/NF-κB pathway.

机构信息

Department of Orthopedic Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264100, Shandong, China.

Department of Orthopedic Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 264100, Shandong, China.

出版信息

Life Sci. 2020 Dec 15;263:118485. doi: 10.1016/j.lfs.2020.118485. Epub 2020 Oct 2.

DOI:10.1016/j.lfs.2020.118485
PMID:33017573
Abstract

AIMS

Sulforaphene (SFE), a naturally occurring isothiocyanate found in cruciferous vegetables, has attracted increasing attention for its anti-cancer effect in many cancers.

MAIN METHODS

We explored the therapeutic effects of SFE in modulating the progression of osteosarcoma. CCK8 assay, colony formation assay, western blot, wounding healing assay and transwell assay were conducted to detect the proliferation, apoptosis, migration and invasion of osteosarcoma cells (U2OS and Saos2) treated with different concentrations of SFE. In addition, tumor xenograft in nude mice is performed to test the effects of SFE in tumorigenesis in vivo. Moreover, the levels of FSTL1 and NF-κB were determined by western blot, and loss of functions of FATL1 and NF-κB were further conducted to evaluate the underlying mechanisms of SFE on osteosarcoma development.

KEY FINDINGS

The results revealed that SFE inhibited the growth while promoted apoptosis of U2OS and Saos2 cells in a dose-dependent manner. Mechanistically, SFE significantly inhibited the expression of NF-κB and FSTL1. However, the genetic intervention of FSTL1 or pharmacologically inhibiting NF-κB weakened the anti-tumor role of SFE.

SIGNIFICANCE

This study suggested that SFE alleviates the progression of osteosarcoma through modulating the FSTL1/NF-κB pathway.

摘要

目的

萝卜硫素(SFE)是十字花科蔬菜中天然存在的异硫氰酸盐,因其在许多癌症中的抗癌作用而受到越来越多的关注。

主要方法

我们探讨了 SFE 调节骨肉瘤进展的治疗效果。通过 CCK8 检测、集落形成检测、Western blot、划痕愈合检测和 Transwell 检测,检测不同浓度 SFE 处理的骨肉瘤细胞(U2OS 和 Saos2)的增殖、凋亡、迁移和侵袭。此外,还在裸鼠中进行肿瘤异种移植实验,以测试 SFE 在体内肿瘤发生中的作用。此外,通过 Western blot 测定 FSTL1 和 NF-κB 的水平,并进一步进行 FATL1 和 NF-κB 的功能丧失实验,以评估 SFE 对骨肉瘤发生发展的潜在机制。

主要发现

结果表明,SFE 呈剂量依赖性抑制 U2OS 和 Saos2 细胞的生长并促进其凋亡。从机制上讲,SFE 显著抑制 NF-κB 和 FSTL1 的表达。然而,FSTL1 的基因干预或抑制 NF-κB 的药物作用削弱了 SFE 的抗肿瘤作用。

意义

本研究表明,SFE 通过调节 FSTL1/NF-κB 通路缓解骨肉瘤的进展。

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