EGFR tyrosine kinase inhibitor AG1478 inhibits cell proliferation and arrests cell cycle in nasopharyngeal carcinoma cells.
Nasopharyngeal carcinoma (NPC), which occurs with a high incidence in southern China and southeast Asia, is of epithelial origin with overexpression of EGF receptor. To study the effect of inhibition of EGFR signaling on nasopharyngeal carcinoma cell proliferation and cell cycle distribution, EGFR tyrosine kinase inhibitor AG1478 was employed to treat Nasopharyngeal Carcinoma CNE2 cells. The results showed that AG1478 inhibited proliferation of CNE2 cells. Immunoblot showed that AG1478 inhibited EGFR phosphorylation in CNE2 cells without reduced expression of EGFR protein. The activation of Akt and MAPK which are downstream molecules of EGFR signaling pathway, were also inhibited by AG1478. AG1478 induced cell cycle arrest in G1 phase, and the levels of protein p27 were significantly up-regulated. We concluded that inhibition of the EGFR signaling induced cell cycle arrest in G1 phase in CNE2 cells and p27 up-regulation was involved in this process. The EGFR kinase specific inhibitor is of potential to be developed into drugs for NPC treatment.
Zhu
X F
XF
Cancer Institute, Cancer Center, Sun Yat-sen University of Medical Sciences, 651 DongFeng Road East, GuangZhou 510060, China.
Liu
Z C
ZC
Xie
B F
BF
Li
Z M
ZM
Feng
G K
GK
Yang
D
D
Zeng
Y X
YX
D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D016193:G1 Phase / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D014407:Tumor Cells, Cultured / Q000187:drug effects; D025521:Tumor Suppressor Proteins; D020032:Tyrphostins / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D025521:Tumor Suppressor Proteins; D020032:Tyrphostins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C101044:RTKI cpd; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases