Cordyceps militaris Fraction Inhibits Angiogenesis of Hepatocellular Carcinoma in vitro and in vivo
Cordyceps militaris Fraction Inhibits Angiogenesis of Hepatocellular Carcinoma in vitro and in vivo
复制标题
北虫草提取物在体外和体内抑制肝细胞癌血管生成
DOI：
10.4103/pm.pm_347_19
复制
发表时间：
2020-01-01
影响因子：
0.7
通讯作者：
Song，Liyan
中科院分区：
文献类型：
--
作者：
Li，Zhiwei;Guo，Zhongyi;Song，Liyan
背景资料：蛹虫草组分（CMF）对慢性粒细胞白血病K562细胞、口腔鳞癌KB细胞的增殖和肺癌细胞的转移均有抑制作用。本研究旨在探讨CMF对肝癌血管生成的抑制作用。目的：本研究的目的是研究CMF在体外和体内对肝癌细胞的抗血管生成作用及其机制。材料与方法：采用Transwell迁移和侵袭实验检测CMF对SMMC-7721细胞和人脐静脉内皮细胞（HUVECs）迁移和侵袭的影响。试管形成和大鼠主动脉环试验用于评估CMF的抗血管生成潜力。免疫荧光和western blot分析检测其抗血管生成的机制。采用SMMC-7721细胞裸鼠移植瘤模型，研究CMF的体内抗血管生成作用及其机制。免疫组化法检测CMF对肿瘤组织中CD 31表达的影响，Western blot法检测肿瘤组织中血管内皮生长因子（VEGF）等相关蛋白的表达。结果如下：CMF可抑制SMMC-7721细胞和HUVECs的迁移和侵袭，抑制VEGF诱导的HUVECs管腔形成和大鼠主动脉环毛细血管形成，并呈浓度依赖性。CMF减弱SMMC-7721细胞和HUVECs中VEGF受体2（VEGFR 2）、Akt和ERK的磷酸化。CMF可显著抑制SMMC-7721细胞裸鼠移植瘤的生长。CMF可降低CD 31的表达水平，Western blot分析显示CMF下调肿瘤组织中VEGFR 2的表达，减弱Akt和ERK的磷酸化，与体外研究结果一致。结论：CMF可抑制肝癌血管生成，其机制与抑制VEGF/VEGFR 2信号通路有关。
Background: Cordyceps militaris fraction (CMF) was found to inhibit the proliferation of chronic myeloid leukemia K562 cells, oral squamous carcinoma KB cells, and the metastasis of lung cancer cells. This study focuses on the activity of CMF against angiogenesis of hepatocellular carcinoma (HCC). Objectives: The objective of the study is to research the antiangiogenic activity of CMF in HCC cells and the underlying mechanism in vitro and in vivo. Materials and Methods: Transwell migration and invasion assays were used to measure the effects of CMF on migration and invasion of SMMC-7721 cells and human umbilical vein endothelial cells (HUVECs). Tube formation and rat aortic ring assays were used to assess the antiangiogenic potential of CMF. The antiangiogenic mechanism was detected by immunofluorescence and western blot analysis. The nude mice xenografted with SMMC-7721 cells were used to study the antiangiogenic activity of CMF and its underlying mechanism in vivo. Immunohistochemistry analysis was used to evaluate the effect of CMF on the expression of CD31, and western blot analysis was also performed to detect the expression of vascular endothelial growth factor (VEGF) and other related proteins in tumor tissues. Results: CMF inhibited the migration and invasion of SMMC-7721 cells and HUVECs and suppressed VEGF-induced tube formation of HUVECs and the formation of aortic ring capillaries of rats in a concentration-dependent manner. CMF attenuated the phosphorylation of VEGF receptor 2 (VEGFR2), Akt, and ERK in SMMC-7721 cells and HUVECs. CMF significantly inhibited tumor growth in nude mice xenografted with SMMC-7721 cells. CMF reduced the expression level of CD31, western blot analysis indicated that CMF downregulated the expression of VEGFR2 and attenuated the phosphorylation of Akt and ERK in the tumor tissues, which was consistent with the results obtained from in vitro study. Conclusion: CMF can inhibit the angiogenesis of HCC and the mechanism is associated with suppression of the VEGF/VEGFR2 signaling pathway.