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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kannadka, Chandrika Aigner, Elmar Moder, Angelika Kanashiro, Celia A. Datz, Christian Hohla, Florian Baker, Benjamin Halmos, Gabor Schally, Andrew V. Buchholz, Stefan |
| Description | Author Affiliation: Hohla F ( Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, LA 70112, USA.); |
| Abstract | Bombesin (BN) or gastrin-releasing peptide (GRP) can stimulate the growth of neoplasms such as breast cancer and small-cell lung carcinoma (SCLC). Antagonists of BN/GRP have been shown to inhibit these cancers. We evaluated whether antagonists of BN/GRP can suppress the growth of human non-SCLC (NSCLC) xenografted into nude mice. The effect of the administration of BN/GRP antagonist RC-3940-II on the growth of H460 and A549 NSCLC cell lines orthotopically xenografted into the intrapulmonary interstitium was examined. Protein levels of K-Ras, COX-2, Akt/pAkt, WT p53, Erk1/2, and lung resistance-related protein (LRP) in tumors were analyzed by Western blot analaysis, and receptors for BN/GRP were investigated by radioligand-binding studies. The effect of RC-3940-II on the proliferation of H460 and A549 cells in vitro was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. High-affinity receptors for BN/GRP were found on tumors. Treatment with RC-3940-II significantly (P < 0.001) inhibited growth of H460 and A549 NSCLC xenografts by 30-50% and led to an improved performance status, compared with controls. In H460 NSCLC, the antitumor effect was associated with a significant (P < 0.001) reduction in protein levels of K-Ras, COX-2, pAkt, and pERK1/2 and with a major augmentation in the expression of WT p53, compared with controls. In A549 NSCLC, pAkt and LRP were significantly down-regulated. Our findings demonstrate the efficacy of BN/GRP antagonist RC-3940-II for the treatment of NSCLC. The suppression of K-Ras, COX-2, pAkt, and LRP, as well as the up-regulation of WT p53 might contribute to the antitumor action of BN/GRP antagonists. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 47 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Bombesin Antagonists & Inhibitors Carcinoma, Non-Small-Cell Lung Enzymology Cyclooxygenase 2 Metabolism Gastrin-Releasing Peptide Lung Neoplasms Proto-Oncogene Proteins C-akt Ras Proteins Animals Analogs & Derivatives Therapeutic Use Drug Therapy Pathology Cell Line, Tumor Cell Proliferation Disease Progression Mice Mice, Nude Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Peptide Fragments Phosphorylation Drug Effects Receptors, Bombesin Tumor Suppressor Protein P53 Xenograft Model Antitumor Assays Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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