Gefitinib Inhibits the Proliferation of Pancreatic Cancer Cells via Cell Cycle Arrest

被引：37
作者：
Zhou, Xiaohua [1 ]
Zheng, Maqing [1 ]
Chen, Fang [1 ]
Zhu, Yunxia [1 ]
Yong, Wei [1 ]
Lin, Haiyan [1 ]
Sun, Yujie [1 ]
Han, Xiao [1 ]
机构：
[1] Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Dept Biochem & Mol Biol, Nanjing 210029, Peoples R China
来源：
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY | 2009年 / 292卷 / 08期
关键词：
gefitinib; pancreatic cancer; cell cycle; aurora B; p27(Kip1); GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; AURORA-B; MOLECULAR-MECHANISMS; G(1) ARREST; EXPRESSION; P27(KIP1); CARCINOMA; ZD1839; IRESSA;
D O I：
10.1002/ar.20938
中图分类号：
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号：
100101 ;
摘要：
High expression of the epidermal growth factor receptor (EGFR) has been implicated in the development of pancreatic cancer. Gefitinib is an orally active and selective EGFR-TKI (EGFR-tyrosine kinase inhibitor) that blocks signal transduction pathways responsible for the proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. This study investigated the anticancer effect of gefitinib on human pancreatic cancer cells and the molecular mechanism involved. We first evaluated the effect of gefitinib on cell proliferation with MTT assay and the results demonstrated that gefitinib significantly inhibited the proliferation of pancreatic cancer cells. Flow cytometric analysis showed that gefitinib induced a delay in cell cycle progression and a G0/G1 arrest together with a G2/M block; these were associated with increased expression of p27(Kip1) cyclin-dependent kinase inhibitor combined with decreased expression of aurora B. Besides, luciferase reporter assay revealed that transcriptional mechanism was responsible for the down-regulation of aurora B protein by gefitinib. Overall, the results suggest a mechanistic connection among these events to provide new insights into the mechanism underlying the antiproliferative effect of gefitinib on pancreatic cancer and supplement a theory basis of gefitinib in clinical treatment of pancreatic cancer. Anat Rec, 292:1122-1127, 2009. (C) 2009 Wiley-Liss, Inc.
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页码：1122 / 1127
页数：6
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