隐丹参酮抗肿瘤及抗血管生成活性研究
Study on anti-tumor and anti-angiogenic activity of cryptotanshinone
冯金红 1郑婷 1侯召华 1吕翠 1王泉博 1张浩 1张宛俊 1魏云波1
作者信息
- 1. 山东省科学院,山东省分析测试中心,山东济南250014
- 折叠
摘要
目的 研究隐丹参酮(Cryptotanshinone)的抗肿瘤活性及其抗血管生成的活性机制,为隐丹参酮治疗肿瘤提供数据支持.方法 培养结肠癌细胞株HCT116、乳腺癌细胞株MDA-MB-231、肺癌细胞株A549、前列腺癌细胞株PC-3,透明卵巢癌ES-2细胞5种肿瘤细胞.将不同浓度梯度的隐丹参酮(200、40、8、1.6、0.32μg/mL)分别与5种肿瘤细胞共培养48 h,采用MTT实验评价隐丹参酮的抗肿瘤活性.选取在抗肿瘤活性最强的细胞,采用流式分析其细胞周期的转变,Transwell检测细胞侵袭情况.采用人脐静脉内皮细胞(HUVEC)评价隐丹参酮抑制血管生成的活性及其对磷酸化的VEGFR1、VEGFR2蛋白的调控作用.结果 在5种肿瘤细胞中,隐丹参酮对乳腺癌细胞株MDA-MB-231抗肿瘤活性最强.细胞周期分析的结果显示隐丹参酮主要能阻断MDA-MB-231细胞于G0/G1期,隐丹参酮能显著抑制MDA-MB-231细胞侵袭(P<0.01),且在不同浓度的隐丹参酮处理下,其抑制侵袭的能力呈浓度依赖性(P<0.01).隐丹参酮能抑制血管生成,此外隐丹参酮能显著抑制血管内皮细胞中VEGFR1、VEGFR2的磷酸化水平.特别是在10μM和20μM浓度下,其抑制活性更为显著.结论 隐丹参酮具有抗肿瘤和抗血管生成的活性,可望成为一种治疗肿瘤的新策略.
Abstract
Objective To study the antitumor activity of cryptotanshinone and its mechanism of anti-angiogenic activity, providing a data for the treatment of cryptotanshinone on tumors.Methods Five kinds of tumor cells were cultured, such as colon cancer cell line HCT116, breast cancer cell line MDA-MB-231, lung cancer cell line A549, prostate cancer cell line PC-3 and clear ovarian cancer ES-2 cell.MTT assay was used to evaluate the anti-tumor effect of cryptotanshinone after co-culture with five concentrations (200, 40, 8, 1.6, 0.32 μg/mL).The cell cycle was detected by flow cytometry.Transwell assay was used to detect the effect of cell invasion.Human umbilical vein endothelial cells ( HUVEC ) were selected to further evaluate the inhibitory effect of cryptotanshinone on angiogenesis and its regulation of phosphorylated VEGFR1 and VEGFR2 proteins.Results Among the five tumor cells, cryptotanshinone had the strongest anti-tumor activity against breast cancer cell line MDA-MB-231.Cell cycle analysis showed that cryptotanshinone significantly blocked the MDA-MB-231 cells in G0/G1 phase, and cryptotanshinone significantly inhibited MDA-MB-231 cell invasion (P<0.01), the ability to inhibit the invasion was in a concentration-dependent manner at different concentrations of cryptotanshinone (P<0.01).In addition,cryptotanshinone can inhibit angiogenesis, and can significantly inhibit the phosphorylation levels of VEGFR1 and VEGFR2 in vascular endothelial cells.In particular, the inhibitory activity was more pronounced at concentrations of 10 μM and 20 μM.Conclusion Cryptotanshinone has anti-tumor and anti-angiogenic activity, is expected to become a new strategy for the treatment of cancer.
关键词
隐丹参酮/抗肿瘤/抗血管生成Key words
cryptotanshinone/anti-tumor/anti-angiogenesis引用本文复制引用
基金项目
国家自然科学基金(81601441)
山东省自然科学基金(ZR2014YL001)
山东省自然科学基金(ZR2015YL005)
山东省自然科学基金(BS2015YY023)
出版年
2017
NETL
NSTL
维普
万方数据