腺病毒介导人内皮抑素基因瘤内注射抑制鼻咽癌生长.pdf

Int. J. Cancer: 121, 2095–2104 (2007) 2007 Wiley-Liss, Inc. Induction of cell cycle arrest and apoptosis in human nasopharyngeal carcinoma cells by ZD6474, an inhibitor of VEGFR tyrosine kinase with additional activity against EGFR tyrosine kinase Xia Xiao1, Jiangxue Wu1*, Xiaofeng Zhu1, Peng Zhao1, Jinlin Zhou1, Quentin Qiang Liu1, Limin Zheng1, Musheng Zeng1, Ranyi Liu1 and Wenlin Huang1,2,3* 1State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, People’s Republic of China 2Institute of Microbiology, Chinese Academy of Science, Beijing 100080, People’s Republic of China 3Guangzhou Doublle Bio-product Inc., Guangzhou 516003, People’s Republic of China ZD6474 is a vascular endothelial growth factor receptor (VEGFR) 17.7 lM.10 It seems that the direct antiproliferative effect of and epidermal growth factor receptor (EGFR) tyrosine kinase in- ZD6474 is highly tissue- and cell-type speci?c. Thus, elucidation hibitor. The present study was undertaken to investigate the direct of the mechanisms underlying the direct antitumor effects of antiproliferative effect of ZD6474 on human nasopharyngeal car- ZD6474 on particular cancer cells may provide an opportunity to cinoma (NPC) in vitro and the antitumor activity on NPC xeno- grafts in vivo. Results indicated that ZD6474 treatment inhibited target speci?c patient subsets who may obtain further bene?t from EGFR phosphorylation and led to a dose- and time-dependent this pharmacological activity. decrease in NPC cell (CNE-1, CNE-2 and C666-1) proliferation. Nasopharyngeal carcinoma (NPC) is a major malignant disease Further investigation demonstrated G0/G1 cell cycle arrest in all of the head/neck region that is endemic within the young popula- 3 cell lines, which was associated with an upregulation of p21 and/ tion of South China and Southeast Asia. The current treatment reg- or p27, and downregulation of CDK4, CDK6 and CDK2. ZD6