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隐丹参酮通过抑制信号转导和转录激活因子3（STAT3）的激活在体外和体内抑制食管鳞状细胞癌。

Cryptotanshinone inhibits esophageal squamous-cell carcinoma in vitro and in vivo through the suppression of STAT3 activation.

作者信息

Ji Yubin, Liu Yichen, Xue Nina, Du Tingting, Wang Liyuan, Huang Rui, Li Ling, Yan Chunhong, Chen Xiaoguang

机构信息

Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, People's Republic of China.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China,

出版信息

Onco Targets Ther. 2019 Jan 29;12:883-896. doi: 10.2147/OTT.S187777. eCollection 2019.

DOI:10.2147/OTT.S187777
PMID:30774375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6357882/
Abstract

PURPOSE

Esophageal squamous-cell carcinoma (ESCC) is the most common subtype of esophageal cancer, with a poor clinical outcome. Cryptotanshinone (CTS) is the main bioactive compound from the root of Bunge. Our study aimed to investigate the anti-cancer effects and molecular mechanisms of CTS on ESCC.

MATERIALS AND METHODS

We investigated the anti-tumor activity of CTS on ESCC in vitro and in vivo. Activation of the STAT3 signaling pathway was evaluated in ESCC and HEK-Blue™ IL-6 cells. Cell viability was assessed by the MTT assay. Apoptosis and cell cycle arrest were assessed using flow cytometry. Cell migration was detected by a scratch wound assay.

RESULTS

CTS inhibited STAT3 expression and IL-6-mediated STAT3 activation in esophageal cancer cells. Subsequently, CTS dose-dependently inhibited the proliferation of esophageal cancer cells via induction of cell apoptosis. Furthermore, CTS suppressed the migration of esophageal cancer cells. In vivo, CTS inhibited tumor growth of EC109 cell in xenograft mice without any obvious effect on body weight.

CONCLUSION

Our results indicated that STAT3 inhibition may be a therapeutic target for esophageal cancer. CTS could provide a potential approach for esophageal cancer therapy by influencing the janus kinase-2/STAT3 signaling pathway.

摘要

目的

食管鳞状细胞癌（ESCC）是食管癌最常见的亚型，临床预后较差。隐丹参酮（CTS）是丹参根中的主要生物活性化合物。本研究旨在探讨CTS对ESCC的抗癌作用及其分子机制。

材料与方法

我们在体外和体内研究了CTS对ESCC的抗肿瘤活性。在ESCC和HEK-Blue™ IL-6细胞中评估STAT3信号通路的激活情况。通过MTT法评估细胞活力。使用流式细胞术评估细胞凋亡和细胞周期阻滞。通过划痕试验检测细胞迁移。

结果

CTS抑制食管癌细胞中STAT3的表达以及IL-6介导的STAT3激活。随后，CTS通过诱导细胞凋亡剂量依赖性地抑制食管癌细胞的增殖。此外，CTS抑制食管癌细胞的迁移。在体内，CTS抑制异种移植小鼠中EC109细胞的肿瘤生长，对体重没有明显影响。

结论

我们的结果表明，抑制STAT3可能是食管癌的一个治疗靶点。CTS可能通过影响janus激酶2/STAT3信号通路为食管癌治疗提供一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/601c968503e1/ott-12-883Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/94ab9c533e6d/ott-12-883Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/23c9938e61fb/ott-12-883Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/142b725049f0/ott-12-883Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/306bb70a2f8f/ott-12-883Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/bd46ecf70334/ott-12-883Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/124765a5be4b/ott-12-883Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/9c4073b84744/ott-12-883Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/601c968503e1/ott-12-883Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/94ab9c533e6d/ott-12-883Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/23c9938e61fb/ott-12-883Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/142b725049f0/ott-12-883Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/306bb70a2f8f/ott-12-883Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/bd46ecf70334/ott-12-883Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/124765a5be4b/ott-12-883Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/9c4073b84744/ott-12-883Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85c2/6357882/601c968503e1/ott-12-883Fig8.jpg

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