p38 MAPK is required for the antitumor activity of the vascular disrupting agent DMXAA1

摘要：

　　5,6-dimethylxanthenone-4-acetic acid (DMXAA),a potent vascular disrupting agent,selectively destroys established tumor vasculature,causing a rapid collapse in blood flow that ultimately leads to inhibition of tumor growth.Here,we demonstrate that p38 MAPK is critically involved in DMXAA-induced cytoskeleton reorganization in endothelial cells and TNF-α production in macrophages,both of which were essential for DMXAA-induced vascular disruption.Inhibition of p38 MAPK significantly attenuated DMXAA-induced actin cytoskeleton reorganization in human umbilical vein endothelial cells and TNF-α production in macrophages.In vivo,p38 MAPK inhibition attenuated the immediate reduction in tumor blood flow induced by DMXAA treatment (<30 min) by inhibiting actin cytoskeleton reorganization in tumor vascular endothelial cells,and blunted the long-lasting (>4 h) DMXAA-induced shutdown of the tumor vasculature by inhibiting intratumoral TNF-α production.These results indicate that p38 MAPK plays a critical role in DMXAA-induced endothelial cell cytoskeleton reorganization and TNF-α production,thus regulating DMXAA-induced antitumor activity.

作者: Qiong Wu Haitian Quan Yongping Xu Yun Li Youhong Hu Liguang Lou

作者单位: Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

会议类型: 国内会议

会议名称: 2012医学科学前沿暨第二届个体化治疗与抗肿瘤药物研究新趋向研讨会

会议地点: 深圳

会议语种:英文

页码: 66-89

在线出版日期: 2012-07-13（万方平台首次上网日期，不代表论文的发表时间）