Lu Jinchang, Luo Qiang, Cheng Ping, Liu Xianjun, Bai Ming, Tu Mingli
Department of Respiratory Medicine, Union Hospital, the First Affiliated Hospital of Tongji Medical College, Huazhong Science and Technology University, Wuhan 430030, China; Department of Respiratory Medicine, Taihe Hospital, the First Affiliated Hospital of Yunyang Medical College, Shiyan 442000, China.
Zhongguo Fei Ai Za Zhi. 2009 Jul 20;12(7):747-52. doi: 10.3779/j.issn.1009-3419.2009.07.002.
Matrine, one of the major alkaloid components of the traditional Chinese medicine Sophora roots, has a wide range of pharmacological effects including anti-inflammatory activities, growth inhibition and induction of cell differentiation and apoptosis. Motigen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) has found to be a crucial signaling pathway in endothelial cells. The aim of this study is to investigate the role of Matrine and MAPK/ERK signal transduction in the inhibition of the proliferation and migration of human umbilical veins endothelial cells (HUVECs) induced by lung cancer cells.
HUVECs were cultured with A549CM. Mat or PD98059 (i.e PD), specific inhibitor of MAPK/ERK, was added into the A549CM. The proliferation of the HUVECs was measured by cell counting. The migration of the HUVECs was observed by wound healing assay. The expression levels of ERK and p-ERK protein were detected by Western Blot analysis.
On 24 hours after intervention, the A549CM significantly stimulated the proliferation, migration and expression of p-ERK of HUVECs. Compared with the A549CM group, Mat significantly inhibited the proliferation, migration and p-ERK expression of HUVECs induced by A549CM. While PD only decreased the proliferation and p-ERK expression of HUVECs induced by A549CM. PD had no effect in the migration of HUVECs.
The results demonstrated that Mat and PD98059 can effectively decrease proliferation and expression of p-ERK of HUVECs induced by A549CM. Furthermore Mat can also inhibit migration of HUVECs induced by A549CM that did not changed by PD98059. These data implied that suppressing MAPK/ERK signal transduction may play the crucial role in resisting lung cacinoma angiogenesis with Mat.
苦参碱是中药苦参根的主要生物碱成分之一,具有广泛的药理作用,包括抗炎活性、生长抑制以及诱导细胞分化和凋亡。丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)已被发现是内皮细胞中的关键信号通路。本研究旨在探讨苦参碱和MAPK/ERK信号转导在抑制肺癌细胞诱导的人脐静脉内皮细胞(HUVECs)增殖和迁移中的作用。
将HUVECs与A549条件培养基(A549CM)共同培养。将苦参碱(Mat)或MAPK/ERK的特异性抑制剂PD98059(即PD)添加到A549CM中。通过细胞计数法测定HUVECs的增殖情况。通过伤口愈合试验观察HUVECs的迁移情况。通过蛋白质免疫印迹分析检测ERK和磷酸化ERK(p-ERK)蛋白的表达水平。
干预24小时后,A549CM显著刺激了HUVECs的增殖、迁移以及p-ERK的表达。与A549CM组相比,Mat显著抑制了A549CM诱导的HUVECs的增殖、迁移和p-ERK表达。而PD仅降低了A549CM诱导的HUVECs的增殖和p-ERK表达。PD对HUVECs的迁移没有影响。
结果表明,Mat和PD98059可有效降低A549CM诱导的HUVECs的增殖和p-ERK表达。此外,Mat还可抑制A549CM诱导的HUVECs的迁移,而PD98059对此无影响。这些数据表明,抑制MAPK/ERK信号转导可能在苦参碱抗肺癌血管生成中起关键作用。