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白藜芦醇通过抑制 STAT3 磷酸化抑制宫颈癌的生长和转移潜能。

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3 phosphorylation.

机构信息

Hubei Institute of Parkinson's Disease at Xiangyang No. 1 People's Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, People's Republic of China.

Hubei Province Hospital of Traditional Chinese Medicine, Hubei Province Academy of Traditional Chinese Medicine, Wuhan, People's Republic of China.

出版信息

Cancer Med. 2020 Nov;9(22):8685-8700. doi: 10.1002/cam4.3510. Epub 2020 Oct 10.

DOI:10.1002/cam4.3510
PMID:33040485
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7666735/
Abstract

Aberrant signal transducer and activator of transcription 3 (STAT3) signaling promotes the initiation and progression of cancer in humans by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. The role of resveratrol（RES）in inhibiting the STAT3 signaling pathway in vivo, particularly in cervical cancer is still unknown. This study aims to investigate the role of STAT3 and its phosphorylation in RES-mediated suppression of cervical cancer. The effects of RES on cervical cancer were determined by examining tumor tissues, their histological changes, and the volume and weight of tumor tissues grown from HeLa cells injected in female athymic BALB/C nude mice. The structure and target interaction of RES were virtually screened using the molecular docking program Autodock Vina. The status of phosphorylated STAT3, protein levels of epithelial-mesenchymal transition molecular markers and extracellular matrix degradation enzymes were determined through Western blot. We demonstrated that RES could suppress the proliferation and metastatic potential of cervical cancer cells by inactivating phosphorylation of STAT3 at Tyr705 but not Ser727. This effect was intensified by inhibition of the STAT3 signal pathway.

摘要

异常信号转导子和转录激活子 3（STAT3）信号通过抑制细胞凋亡或诱导细胞增殖、血管生成、侵袭和转移，促进人类癌症的发生和发展。白藜芦醇（RES）在体内抑制 STAT3 信号通路的作用，特别是在宫颈癌中的作用尚不清楚。本研究旨在探讨 STAT3 及其磷酸化在 RES 介导的宫颈癌抑制中的作用。通过检查肿瘤组织、组织学变化以及从注射到雌性无胸腺 BALB/C 裸鼠中的 HeLa 细胞中生长的肿瘤组织的体积和重量，来确定 RES 对宫颈癌的影响。使用分子对接程序 Autodock Vina 对 RES 的结构和靶标相互作用进行了虚拟筛选。通过 Western blot 确定磷酸化 STAT3 的状态、上皮-间充质转化分子标志物和细胞外基质降解酶的蛋白水平。我们表明，RES 通过使 STAT3 在 Tyr705 处的磷酸化失活来抑制宫颈癌细胞的增殖和转移潜力，但不会抑制 Ser727。这种作用通过抑制 STAT3 信号通路得到加强。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/e227b081ba79/CAM4-9-8685-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/102a4d860f6c/CAM4-9-8685-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/6b223b7a04ef/CAM4-9-8685-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/94a629bd0006/CAM4-9-8685-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/e227b081ba79/CAM4-9-8685-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/2b5d1089a421/CAM4-9-8685-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/f976752436e0/CAM4-9-8685-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30ee/7666735/102a4d860f6c/CAM4-9-8685-g005.jpg
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