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丹参酮 I 通过抑制 JAK/STAT3 信号通路抑制骨肉瘤的生长和转移。

Tanshinone I inhibits the growth and metastasis of osteosarcoma via suppressing JAK/STAT3 signalling pathway.

机构信息

Department of Orthopaedics, The Third Xiangya Hospital of Central South University, Changsha, China.

出版信息

J Cell Mol Med. 2019 Sep;23(9):6454-6465. doi: 10.1111/jcmm.14539. Epub 2019 Jul 10.

DOI:10.1111/jcmm.14539
PMID:31293090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6714145/
Abstract

Tanshinone I (Tan I) is a widely used diterpene compound derived from the traditional Chinese herb Danshen. Increasing evidence suggests that it exhibits anti-cancer activity in various human cancers. However, the in vitro and in vivo effects of Tan I on osteosarcoma (OS) remain inadequately elucidated, especially those against tumour metastasis. Our results showed that Tan I significantly inhibited OS cancer cell proliferation, migration and invasion and induced cell apoptosis in vitro. Moreover, treatment with 10 and 20 mg/kg Tan I effectively suppressed tumour growth in subcutaneous xenografts and orthotopic xenograft mouse models. In addition, Tan I significantly inhibited tumour metastasis in intracardiac inoculation xenograft models. The results also showed that Tan I-induced increased expression of the proapoptotic gene Bax and decreased expression of the anti-apoptotic gene Bcl-2 is the possible mechanism of its anti-cancer effects. Tan I was also found to abolish the IL-6-mediated activation of the JAK/STAT3 signalling pathway. Conclusively, this study is the first to show that Tan I suppresses OS growth and metastasis in vitro and in vivo, suggesting it may be a potential novel and efficient drug candidate for the treatment of OS progression.

摘要

丹参酮 I(Tan I)是一种广泛应用的二萜化合物,来源于传统中药丹参。越来越多的证据表明,它在各种人类癌症中表现出抗癌活性。然而,Tan I 对骨肉瘤(OS)的体外和体内作用仍未得到充分阐明,特别是针对肿瘤转移的作用。我们的研究结果表明,Tan I 可显著抑制 OS 癌细胞的增殖、迁移和侵袭,并诱导细胞凋亡。此外,10 和 20mg/kg 的 Tan I 治疗可有效抑制皮下异种移植和原位异种移植小鼠模型中的肿瘤生长。此外,Tan I 可显著抑制心脏内接种异种移植模型中的肿瘤转移。结果还表明,Tan I 诱导的促凋亡基因 Bax 表达增加和抗凋亡基因 Bcl-2 表达减少是其抗癌作用的可能机制。研究还发现,Tan I 可消除 IL-6 介导的 JAK/STAT3 信号通路的激活。综上所述,本研究首次表明 Tan I 可抑制 OS 的体内外生长和转移,提示其可能是治疗 OS 进展的一种有潜力的新型高效药物候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/dfd118264437/JCMM-23-6454-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/c98549f46aa1/JCMM-23-6454-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/d594acda6ad8/JCMM-23-6454-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/c0f4c70d77da/JCMM-23-6454-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/3117d266406f/JCMM-23-6454-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/dfd118264437/JCMM-23-6454-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/c98549f46aa1/JCMM-23-6454-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/d594acda6ad8/JCMM-23-6454-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/c0f4c70d77da/JCMM-23-6454-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/3117d266406f/JCMM-23-6454-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c7a/6714145/dfd118264437/JCMM-23-6454-g005.jpg

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