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Antiproliferative effect of growth hormone-releasing hormone (GHRH) antagonist on ovarian cancer cells through the EGFR-Akt pathway Guo, Jian; Schally, Andrew V.; Zarandi, Marta; Varga, Jozsef; Leung, P. C. K.
Abstract
Background: Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers. Methods: MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR. Results: In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV)1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR) level and the phosphorylation of Akt (p-Akt), suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells. Conclusions: The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.
Item Metadata
Title |
Antiproliferative effect of growth hormone-releasing hormone (GHRH) antagonist on ovarian cancer cells through the EGFR-Akt pathway
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Creator | |
Contributor | |
Publisher |
BioMed Central
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Date Issued |
2010-05-28
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Description |
Background:
Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers.
Methods:
MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR.
Results:
In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV)1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR) level and the phosphorylation of Akt (p-Akt), suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells.
Conclusions:
The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.
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Genre | |
Type | |
Language |
eng
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Date Available |
2016-01-06
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution 4.0 International (CC BY 4.0)
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DOI |
10.14288/1.0223097
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URI | |
Affiliation | |
Citation |
Reproductive Biology and Endocrinology. 2010 May 28;8(1):54
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Publisher DOI |
10.1186/1477-7827-8-54
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Peer Review Status |
Reviewed
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Scholarly Level |
Faculty
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Copyright Holder |
Guo et al.
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution 4.0 International (CC BY 4.0)