摘要
背景与目的苦参碱是中国传统中药槐根的主要生物碱成分之一,具有抗炎、抑制肿瘤细胞增殖、诱导肿瘤细胞分化和凋亡等作用。丝裂原活化蛋白激酶/细胞外调节蛋白激酶(Motigen-activated proteinkinase/extracelluar regulated protein kinase,MAPK/ERK)级联通路是血管内皮细胞信号转导的重要途径。本研究目的是探讨苦参碱(Matrine,Mat)和MAPK/ERK信号转导通路在抑制肺腺癌A549细胞条件培养基(A549human lung cancer cells conditioned medium,A549CM)诱导的人脐静脉内皮细胞(human umbilical veins endothelial cells,HUVECs)增殖和迁移中的作用。方法应用Mat与MAPK/ERK特异性抑制剂PD98059(PD)处理A549CM培养的HUVECs,采用细胞计数、划痕损伤实验和Western Blot技术,观察Mat、PD98059对A549CM诱导的人脐静脉内皮细胞增殖、迁移及磷酸化ERK(p-ERK)表达的影响。结果干预后24h,与对照组相比,A549CM显著促进HUVECs增殖、迁移及p-ERK的表达。与A549CM组相比,Mat能明显抑制A549CM诱导的HUVECs增殖和迁移及p-ERK的表达;PD98059可以抑制HUVECs增殖及p-ERK表达,而对迁移没有作用。结论Mat和PD98059均能有效抑制A549CM诱导的HUVECs增殖和p-ERK表达,Mat还能抑制A549CM诱导的HUVECs迁移,而PD98059对A549CM诱导的HUVECs迁移没有影响,提示抑制MAPK/ERK信号传导通路可能是苦参碱抗肺癌血管生成的部分机制。
Background and objective 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 ceils. 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 en- dothelial cells （HUVECs） induced by lung cancer cells. Methods HUVECs were cultured with A549CM. Mat or PD98059 （i.e PD）, specific inhibitor of MAPK/ERK, was added into the AS49CM. 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. Results On 24 hours after intervention, the AS49CM 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 A.549CM. PD had no effect in the migration of HUVECs. Conclusion The results demonstrated that Mat and PD98059 can effectively decrease proliferation and expression ofp-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.
出处
《中国肺癌杂志》
CAS
2009年第7期747-752,共6页
Chinese Journal of Lung Cancer
基金
湖北省教育厅重点项目(No.B200524009)资助~~
