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.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology*
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Cell Cycle / physiology
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Cell Line, Tumor
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Cell Survival / drug effects
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ErbB Receptors / antagonists & inhibitors
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ErbB Receptors / metabolism
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Flow Cytometry
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Humans
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Imidazoles / pharmacology*
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Microscopy, Confocal
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Dynamics Simulation
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Phosphorylation / drug effects
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Quinazolines / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Imidazoles
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Quinazolines
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EGFR protein, human
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ErbB Receptors
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Mitogen-Activated Protein Kinases