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TGF-β 抑制剂 RepSox 通过 JNK/Smad3 信号通路抑制骨肉瘤。

TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway.

机构信息

Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, P.R. China.

Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China.

出版信息

Int J Oncol. 2021 Nov;59(5). doi: 10.3892/ijo.2021.5264. Epub 2021 Sep 17.

DOI:10.3892/ijo.2021.5264
PMID:34533199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8460063/
Abstract

Osteosarcoma (OS) is the most common malignant bone tumor and the long‑term survival rates remain unsatisfactory. Transforming growth factor‑β (TGF‑β) has been revealed to play a crucial role in OS progression, and RepSox is an effective TGF‑β inhibitor. In the present study, the effect of RepSox on the proliferation of the OS cell lines (HOS and 143B) was detected. The results revealed that RepSox effectively inhibited the proliferation of OS cells by inducing S‑phase arrest and apoptosis. Moreover, the inhibitory effect of RepSox on cell migration and invasion was confirmed by wound‑healing and Transwell assays. Furthermore, western blotting revealed that the protein levels of molecules associated with the epithelial‑mesenchymal transition (EMT) phenotype, including E‑cadherin, N‑cadherin, Vimentin, matrix metalloproteinase (MMP)‑2 and MMP‑9, were reduced by RepSox treatment. Concurrently, it was also revealed that the JNK and Smad3 signaling pathway was inhibited. Our findings using a xenograft model also revealed that RepSox markedly inhibited the growth of tumors. In general, our data demonstrated that RepSox suppressed OS proliferation, EMT and promoted apoptosis by inhibiting the JNK/Smad3 signaling pathway. Thus, RepSox may be a potential anti‑OS drug.

摘要

骨肉瘤（OS）是最常见的恶性骨肿瘤，其长期生存率仍不尽人意。转化生长因子-β（TGF-β）已被揭示在 OS 进展中起关键作用，RepSox 是一种有效的 TGF-β抑制剂。在本研究中，检测了 RepSox 对 OS 细胞系（HOS 和 143B）增殖的影响。结果表明，RepSox 通过诱导 S 期阻滞和细胞凋亡，有效抑制 OS 细胞的增殖。此外，通过划痕和 Transwell 实验证实了 RepSox 对细胞迁移和侵袭的抑制作用。进一步的 Western blot 结果显示，RepSox 处理降低了与上皮-间充质转化（EMT）表型相关的分子的蛋白水平，包括 E-钙黏蛋白、N-钙黏蛋白、波形蛋白、基质金属蛋白酶（MMP）-2 和 MMP-9。同时，还发现 JNK 和 Smad3 信号通路被抑制。我们使用异种移植模型的研究结果还表明，RepSox 显著抑制了肿瘤的生长。总的来说，我们的数据表明 RepSox 通过抑制 JNK/Smad3 信号通路，抑制 OS 增殖、EMT 并促进细胞凋亡。因此，RepSox 可能是一种潜在的抗 OS 药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/5985cdbe6ab1/IJO-59-05-05264-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/fa2473d0273e/IJO-59-05-05264-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/b0a09560bc84/IJO-59-05-05264-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/866ac16649ff/IJO-59-05-05264-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/1d24ee4b52d3/IJO-59-05-05264-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/4ca58eef1b51/IJO-59-05-05264-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/5985cdbe6ab1/IJO-59-05-05264-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/fa2473d0273e/IJO-59-05-05264-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/b0a09560bc84/IJO-59-05-05264-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/866ac16649ff/IJO-59-05-05264-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/1d24ee4b52d3/IJO-59-05-05264-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/4ca58eef1b51/IJO-59-05-05264-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3592/8460063/5985cdbe6ab1/IJO-59-05-05264-g05.jpg

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