Xiaohua Zhou and Maqing Zheng contributed equally to this work.
Gefitinib Inhibits the Proliferation of Pancreatic Cancer Cells via Cell Cycle Arrest
Article first published online: 30 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
The Anatomical Record
Volume 292, Issue 8, pages 1122–1127, August 2009
How to Cite
Zhou, X., Zheng, M., Chen, F., Zhu, Y., Yong, W., Lin, H., Sun, Y. and Han, X. (2009), Gefitinib Inhibits the Proliferation of Pancreatic Cancer Cells via Cell Cycle Arrest. Anat Rec, 292: 1122–1127. doi: 10.1002/ar.20938
- Issue published online: 30 JUL 2009
- Article first published online: 30 JUL 2009
- Manuscript Accepted: 12 MAY 2009
- Manuscript Received: 8 MAR 2009
- Natural Science Foundation of Jiangsu Province. Grant Number: BK2003003
- pancreatic cancer;
- cell cycle;
- aurora B;
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 p27Kip1 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. © 2009 Wiley-Liss, Inc.