title: Anti-tumor effects of B-2, a novel 2,3-disubstituted 8-arylamino-3H-imidazo[4,5-g]quinazoline derivative, on the human lung adenocarcinoma A549 cell line in vitro and in vivo.
abstract: This study evaluated the selective effects of 2-isopropyl-3-butyl-8-(4-fluorophenylamino)-3H-imidazo[4,5-g]quinazoline (B-2), a member of a series of quinazolines, on the cell survival and growth of the non-small cell lung cancer (NSCLC) cell line A549 in vitro and in vivo. Cytotoxicity assay, hollow fiber assay and cell xenograft model experiment revealed that B-2 showed selective effects on A549 cell survival or growth in a dose-dependent manner. At a dose of 100mg/kg, B-2 showed stronger efficacy on tumor growth inhibition in nude mice than Iressa. Exposure of A549 cells to B-2 caused inhibition of EGFR-dependent ERK-MAPK activation. In addition, inhibition of cell cycle progression and induction of mitochondria-dependent apoptosis might contribute to present the multitarget pathway of non-small cell lung cancer treatment of B-2.
authors.affiliation: Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Ding
authors.forename: Lingyan
authors.initials: L
authors.lastname: Gao
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Ye
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
authors.forename: Yijia
authors.initials: Y
authors.lastname: Lou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases