Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest.
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.
Zhou
Xiaohua
X
Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, People's Republic of China.
Zheng
Maqing
M
Chen
Fang
F
Zhu
Yunxia
Y
Yong
Wei
W
Lin
Haiyan
H
Sun
Yujie
Y
Han
Xiao
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016195:G2 Phase / Q000502:physiology; D000077156:Gefitinib; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*
D000970:Antineoplastic Agents; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011799:Quinazolines; D050760:Cyclin-Dependent Kinase Inhibitor p27; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D000077156:Gefitinib