title: Icotinib, a potent and specific EGFR tyrosine kinase inhibitor, inhibits growth of squamous cell carcinoma cell line A431 through negatively regulating AKT signaling.
abstract: Icotinib is a potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. In this study, we reported that icotinib had the antitumor activity on human squamous cell carcinoma cell line A431 in vitro. Meanwhile, adhesion to fibronectin and expression of integrin α3 and β1 were significantly reduced in a dose-dependent manner after the treatment of icotinib. Moreover, icotinib induced cell cycle arrested and affected expression of various cell cycle related proteins in squamous cancer cell line A431, whereas it did not cause apoptosis. Furthermore, icotinib remarkably down-regulated phosphorylation of protein kinase B (AKT) though blocking the interaction between 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in A431 cells. Taken together, it is shown that the small molecular compound, icotinib, has an anti-squamous cell carcinoma activity in vitro and its antitumor mechanism is associated with the blockage of the interaction between PDK1 and AKT. These results provide a novel strategy for anti-squamous cell carcinoma therapy.
authors.affiliation: Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.forename: Peifen
authors.initials: P
authors.lastname: Cai
authors.forename: Xianying
authors.initials: X
authors.lastname: Fang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D043844:Crown Ethers / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D043844:Crown Ethers; C000631429:PDK1 protein, human; C000631433:Pdk1 protein, mouse; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011799:Quinazolines; C531470:icotinib; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt