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丹参酮 I 对人非小细胞肺癌的抗癌作用

Anticancer effects of tanshinone I in human non-small cell lung cancer.

作者信息

Lee Chen-Yu, Sher Hui-Fang, Chen Huei-Wen, Liu Chun-Chi, Chen Ching-Hsien, Lin Choun-Sea, Yang Pan-Chyr, Tsay Hsin-Sheng, Chen Jeremy J W

机构信息

Institutes of Biomedical Sciences and Molecular Biology, National Chung-Hsing University, Taichung, Taiwan 40227, Republic of China.

出版信息

Mol Cancer Ther. 2008 Nov;7(11):3527-38. doi: 10.1158/1535-7163.MCT-07-2288.

Abstract

Tanshinones are the major bioactive compounds of Salvia miltiorrhiza Bunge (Danshen) roots, which are used in many therapeutic remedies in Chinese traditional medicine. We investigated the anticancer effects of tanshinones on the highly invasive human lung adenocarcinoma cell line, CL1-5. Tanshinone I significantly inhibited migration, invasion, and gelatinase activity in macrophage-conditioned medium-stimulated CL1-5 cells in vitro and also reduced the tumorigenesis and metastasis in CL1-5-bearing severe combined immunodeficient mice. Unlike tanshinone IIA, which induces cell apoptosis, tanshinone I did not have direct cytotoxicity. Real-time quantitative PCR, luciferase reporter assay, and electrophoretic mobility shift assay revealed that tanshinone I reduces the transcriptional activity of interleukin-8, the angiogenic factor involved in cancer metastasis, by attenuating the DNA-binding activity of activator protein-1 and nuclear factor-kappaB in conditioned medium-stimulated CL1-5 cells. Microarray and pathway analysis of tumor-related genes identified the differentially expressed genes responding to tanshinone I, which may be associated with the Ras-mitogen-activated protein kinase and Rac1 signaling pathways. These results suggest that tanshinone I exhibits anticancer effects both in vitro and in vivo and that these effects are mediated at least partly through the interleukin-8, Ras-mitogen-activated protein kinase, and Rac1 signaling pathways. Although tanshinone I has a remarkable anticancer action, its potential anticoagulant effect should be noted and evaluated.

摘要

丹参酮是丹参根中的主要生物活性化合物,在许多中药治疗中都有应用。我们研究了丹参酮对高侵袭性人肺腺癌细胞系CL1-5的抗癌作用。丹参酮I在体外显著抑制巨噬细胞条件培养基刺激的CL1-5细胞的迁移、侵袭和明胶酶活性,并且还减少了携带CL1-5的严重联合免疫缺陷小鼠的肿瘤发生和转移。与诱导细胞凋亡的丹参酮IIA不同,丹参酮I没有直接的细胞毒性。实时定量PCR、荧光素酶报告基因检测和电泳迁移率变动分析表明,丹参酮I通过减弱条件培养基刺激的CL1-5细胞中激活蛋白-1和核因子-κB的DNA结合活性,降低了参与癌症转移的血管生成因子白细胞介素-8的转录活性。肿瘤相关基因的微阵列和通路分析确定了对丹参酮I有反应的差异表达基因,这些基因可能与Ras-丝裂原活化蛋白激酶和Rac1信号通路有关。这些结果表明,丹参酮I在体外和体内均表现出抗癌作用,且这些作用至少部分是通过白细胞介素-8、Ras-丝裂原活化蛋白激酶和Rac1信号通路介导的。尽管丹参酮I具有显著的抗癌作用,但应注意并评估其潜在的抗凝作用。

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