Rick, Ferenc G. and Buchholz, Stefan and Schally, Andrew V. and Szalontay, Luca and Krishan, Awtar and Datz, Christian and Stadlmayr, Andreas and Aigner, Elmar and Perez, Roberto and Seitz, Stephan and Block, Norman L. and Hohla, Florian (2012) Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. CELL CYCLE, 11 (13). pp. 2518-2525. ISSN 1538-4101,
Full text not available from this repository. (Request a copy)Abstract
We investigated the efficacy of a powerful antagonist of bombesin/gastrin-releasing peptide (BN/GRP) RC-3940-II administered as a single agent or in combination with cytotoxic agents on the growth of HT-29, HCT-116 and HCT-15 human colon cancer in vitro and in vivo. GRP-receptor mRNA and protein were found in all three cell lines tested. Exposure of HT-29 cells to 10 mu M RC-3940-II led to an increase in the number of cells blocked in S phase and G(2)/M and cells with lower G(0)/G(1) DNA content. Similar changes on the cell cycle traverse of HT-29 cells could also be seen at lower concentrations of RC-3940-II (1 mu M) after pretreatment with 100 nM GRP (14-27), indicating a dose-dependent mechanism of action based on the blockage of BN/GRP induced proliferation of tumor cells at lower concentrations. Daily in vivo treatment with BN/GRP antagonist RC-3940-II decreased the volume of HT-29, HCT-116 and HCT-15 tumors xenografted into athymic nude mice by 25 to 67% (p < 0.005). Combined treatment with RC-3940-II and chemotherapeutic agents 5-FU and irinotecan resulted in a synergistic tumor growth suppression of HT-29, HCT-116 and HCT-15 xenografts by 43% to 78%. In HT-29 and HCT-116 xenografts the inhibition for the combinations of RC-3940-II and irinotecan vs. single substances (p < 0.05) was significantly greater. These findings support the use of RC-3940-II as an anticancer agent and may help to design clinical trials using RC-3940-II in combinations with cytotoxic agents.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METASTATIC COLORECTAL-CANCER; SOMATOSTATIN ANALOG RC-160; CELL LUNG-CARCINOMA; BOMBESIN ANTAGONISTS; FACTOR RECEPTOR; 1ST-LINE TREATMENT; NUDE-MICE; HORMONE; ACTIVATION; EXPRESSION; BN/GRP antagonist; RC-3940-II; colon cancer; cytotoxic agents; 5-FU; irinotecan; targeted therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2020 11:27 |
| Last Modified: | 11 May 2020 11:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18501 |
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