Rick, Ferenc G. and Seitz, Stephan and Schally, Andrew V. and Szalontay, Luca and Krishan, Awtar and Datz, Christian and Stadlmayr, Andreas and Buchholz, Stefan and Block, Norman L. and Hohla, Florian (2012) GHRH antagonist when combined with cytotoxic agents induces S-phase arrest and additive growth inhibition of human colon cancer. CELL CYCLE, 11 (22). pp. 4203-4210. ISSN 1538-4101, 1551-4005
Full text not available from this repository. (Request a copy)Abstract
Treatment of colon cancer with an antagonist of growth hormone-releasing hormone (GHRH), JMR-132, results in a cell cycle arrest in S-phase of the tumor cells. Thus, we investigated the effect of JMR-132 in combination with S-phase-specific cytotoxic agents, 5-FU, irinotecan and cisplatin on the in vitro and in vivo growth of HT-29, HCT-116 and HCT-15 human colon cancer cell lines. In vitro, every compound inhibited proliferation of HCT-116 cells in a dose-dependent manner. Treatment with JMR-132 (5 mu M) combined with 5-FU (1.25 mu M), irinotecan (1.25 mu M) or cisplatin (1.25 mu M) resulted in an additive growth inhibition of HCT-116 cells in vitro as shown by MTS assay. Cell cycle analyses revealed that treatment of HCT-116 cells with JMR-132 was accompanied by a cell cycle arrest in S-phase. Combination treatment using JMR-132 plus a cytotoxic drug led to a significant increase of the sub-G 1 fraction, suggesting apoptosis. In vivo, daily treatment with GHRH antagonist JMR-132 decreased the tumor volume by 40-55% (p < 0.001) of HT-29, HCT-116 and HCT-15 tumors xenografted into athymic nude mice. Combined treatment with JMR-132 plus chemotherapeutic agents 5-FU, irinotecan or cisplatin resulted in an additive tumor growth suppression of HT-29, HCT-116 and HCT-15 xenografts to 56-85%. Our observations indicate that JMR-132 enhances the antiproliferative effect of S-phase-specific cytotoxic drugs by causing accumulation of tumor cells in S-phase.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HORMONE-RELEASING-HORMONE; METASTATIC COLORECTAL-CANCER; BENIGN PROSTATIC HYPERPLASIA; NEGATIVE BREAST CANCERS; SOMATOSTATIN ANALOG; SPLICE VARIANTS; IN-VIVO; SYNERGISTIC INHIBITION; PEPTIDE ANTAGONIST; 1ST-LINE TREATMENT; GHRH antagonist; JMR-132; colon cancer; cytotoxic agents; S-phase arrest; additive growth inhibition; 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: | 04 May 2020 07:51 |
| Last Modified: | 04 May 2020 07:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17805 |
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