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.
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Authors | Zhe Chen, Xin Huang, Hongyu Yang, Wenbo Ding, Lingyan Gao, Ziqi Ye, Yandong Zhang, Yongping Yu, Yijia Lou |
Journal | Chemico-biological interactions
(Chem Biol Interact)
Vol. 189
Issue 1-2
Pg. 90-9
(Jan 15 2011)
ISSN: 1872-7786 [Electronic] Ireland |
PMID | 21075094
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Imidazoles
- Quinazolines
- EGFR protein, human
- ErbB Receptors
- Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, metabolism, pathology)
- Cell Cycle
(physiology)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- ErbB Receptors
(antagonists & inhibitors, metabolism)
- Flow Cytometry
- Humans
- Imidazoles
(pharmacology)
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Microscopy, Confocal
- Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Molecular Dynamics Simulation
- Phosphorylation
(drug effects)
- Quinazolines
(pharmacology)
- Xenograft Model Antitumor Assays
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