scholarly journals Agonists of growth hormone-releasing hormone (GHRH) inhibit human experimental cancers in vivo by down-regulating receptors for GHRH

2018 ◽  
Vol 115 (47) ◽  
pp. 12028-12033 ◽  
Author(s):  
Andrew V. Schally ◽  
Haibo Wang ◽  
Jinlin He ◽  
Renzhi Cai ◽  
Wei Sha ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Hormone ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Growth Hormone Releasing Hormone ◽  
Down Regulation ◽  
Releasing Hormone ◽  
Inhibition Of Tumor Growth

The effects of the growth hormone-releasing hormone (GHRH) agonist MR409 on various human cancer cells were investigated. In H446 small cell lung cancer (SCLC) and HCC827 and H460 (non-SCLC) cells, MR409 promoted cell viability, reduced cell apoptosis, and induced the production of cellular cAMP in vitro. Western blot analyses showed that treatment of cancer cells with MR409 up-regulated the expression of cyclins D1 and D2 and cyclin-dependent kinases 4 and 6, down-regulated p27kip1, and significantly increased the expression of the pituitary-type GHRH receptor (pGHRH-R) and its splice-variant (SV1). Hence, in vitro MR409 exerts agonistic action on lung cancer cells in contrast to GHRH antagonists. However, in vivo, MR409 inhibited growth of lung cancers xenografted into nude mice. MR409 given s.c. at 5 μg/day for 4 to 8 weeks significantly suppressed growth of HCC827, H460, and H446 tumors by 48.2%, 48.7%, and 65.6%, respectively. This inhibition of tumor growth by MR409 was accompanied by the down-regulation of the expression of pGHRH-R and SV1 in the pituitary gland and tumors. Tumor inhibitory effects of MR409 in vivo were also observed in other human cancers, including gastric, pancreatic, urothelial, prostatic, mammary, and colorectal. This inhibition of tumor growth parallel to the down-regulation of GHRH-Rs is similar and comparable to the suppression of sex hormone-dependent cancers after the down-regulation of receptors for luteinizing hormone-releasing hormone (LHRH) by LHRH agonists. Further oncological investigations with GHRH agonists are needed to elucidate the underlying mechanisms.

scholarly journals POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ronggang Luo ◽  
Yi Zhuo ◽  
Quan Du ◽  
Rendong Xiao
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

scholarly journals Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma

2019 ◽  
Vol 116 (6) ◽  
pp. 2226-2231 ◽  
Author(s):  
Tania Villanova ◽  
Iacopo Gesmundo ◽  
Valentina Audrito ◽  
Nicoletta Vitale ◽  
Francesca Silvagno ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Cell Lines ◽  
Malignant Pleural Mesothelioma ◽  
Pleural Mesothelioma ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Ghrh Antagonists

Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with exposure to asbestos, with poor prognosis and no effective therapies. The strong inhibitory activities of growth hormone-releasing hormone (GHRH) antagonists have been demonstrated in different experimental human cancers, including lung cancer; however, their role in MPM remains unknown. We assessed the effects of the GHRH antagonists MIA-602 and MIA-690 in vitro in MPM cell lines and in primary MPM cells, and in vivo in MPM xenografts. GHRH, GHRH receptor, and its main splice variant SV1 were found in all the MPM cell types examined. In vitro, MIA-602 and MIA-690 reduced survival and proliferation in both MPM cell lines and primary cells and showed synergistic inhibitory activity with the chemotherapy drug pemetrexed. In MPM cells, GHRH antagonists also regulated activity and expression of apoptotic molecules, inhibited cell migration, and reduced the expression of matrix metalloproteinases. These effects were accompanied by impairment of mitochondrial activity and increased production of reactive oxygen species. In vivo, s.c. administration of MIA-602 and MIA-690 at the dose of 5 μg/d for 4 wk strongly inhibited the growth of MPM xenografts in mice, along with reduction of tumor insulin-like growth factor-I and vascular endothelial growth factor. Overall, these results suggest that treatment with GHRH antagonists, alone or in association with chemotherapy, may offer an approach for the treatment of MPM.

scholarly journals Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2331
Author(s):  
Chongxu Zhang ◽  
Tengjiao Cui ◽  
Renzhi Cai ◽  
Medhi Wangpaichitr ◽  
Mehdi Mirsaeidi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Therapeutic Potential ◽  
Dependent Manner ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lung Physiology ◽  
Extracellular Signal ◽  
P21 Activated Kinase

Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. GHRH-R antagonists (i.e., synthetic peptides), which we have tested in various models, exert growth-inhibitory effects in lung cancer cells in vitro and in vivo in addition to having anti-inflammatory, anti-oxidative, and pro-apoptotic effects. One antagonist of the GHRH-R used in recent studies reviewed here, MIA-602, lessens both inflammation and fibrosis in a mouse model of bleomycin lung injury. GHRH and its peptide agonists regulate the proliferation of fibroblasts through the modulation of extracellular signal-regulated kinase (ERK) and Akt pathways. In addition to downregulating GH and IGF-1, GHRH-R antagonist MIA-602 inhibits signaling pathways relevant to inflammation, including p21-activated kinase 1-signal transducer and activator of transcription 3/nuclear factor-kappa B (PAK1-STAT3/NF-κB and ERK). MIA-602 induces fibroblast apoptosis in a dose-dependent manner, which is an effect that is likely important in antifibrotic actions. Taken together, the novel data reviewed here show that GHRH is an important peptide that participates in lung homeostasis, inflammation, wound healing, and cancer; and GHRH-R antagonists may have therapeutic potential in lung diseases.

Growth hormone-releasing hormone (GHRH) antagonists increase the sensitivity to radiotherapy in lung cancer cells

2020 ◽  
Author(s):  
Iacopo Gesmundo ◽  
Alessandro Dematteis ◽  
Alessandro Fanciulli ◽  
Giglioli Francesca Romana ◽  
Renzhi Cai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Hormone ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Ghrh Antagonists

Inhibition of proliferation in human MNNG/HOS osteosarcoma and SK-ES-1 Ewing sarcoma cell lines in vitro and in vivo by antagonists of growth hormone-releasing hormone

Cancer ◽  
2002 ◽  
Vol 95 (8) ◽  
pp. 1735-1745 ◽  
Author(s):  
Ryszard Braczkowski ◽  
Andrew V. Schally ◽  
Artur Plonowski ◽  
Jozsef L. Varga ◽  
Kate Groot ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Lines ◽  
Ewing Sarcoma ◽  
Growth Hormone Releasing Hormone ◽  
Sarcoma Cell ◽  
Inhibition Of Proliferation ◽  
Releasing Hormone

Activated interferon signaling by down-regulation of CENP-N contributing to inhibited tumor growth in breast cancer

2019 ◽  
Author(s):  
Zhenhua Zhai ◽  
Ye Zhou ◽  
Xing Liu ◽  
Ying Wang ◽  
Yuyang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Interferon Signaling ◽  
Breast Cancer Patients ◽  
Down Regulation ◽  
Key Factor

Abstract Background Centromere proteins (CENPs) are primary components for chromosomal segregation in the mitotic stage. CENP-N is a member of CENPs, and is a key factor for recruitment of other CENPs and formation of a link between the centromere and micro-tubules, which facilitate cell division. Methods In order to clarify the role of CENP-N in breast cancer, RNA sequences data were downloaded from TCGA online database and the CENP-N expression was knocked down in breast cancer cells. Results The results show that the expression of CENP-N was higher in breast cancer comparing with the paracancerous tissues. In breast cancer, patients with high expression of CENP-N have a short-term overall survival compared with low expression of CENP-N. Both in vitro and in vivo, the growth of breast cancer cells was inhibited by down-regulation of CENP-N. In the gene-chip analysis, it reveals that down-regulation of CENP-N is primarily associated with functions of immune response and anti-tumor ef-fects. Of these changed canonical pathways, the activated interferon signaling was the most significant in CENP-N down-regulated breast cancer cells. In the western blot as-say, up-regulated expressions of molecules involved in interferon signaling were also confirmed. Conclusions Our results suggest that CENP-N can be a potential therapeutic target in the treatment of breast cancer, and the involved interferon signaling needs to be mainly fo-cused on. Keywords: CENP-N, Breast cancer, interferon signaling, Tumor growth

Effect of novel growth hormone-releasing hormone antagonists on growth of experimental renal cell carcinomas.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 469-469 ◽  
Author(s):  
Ferenc Rick ◽  
Luca Szalontay ◽  
Andrew Abi-Chaker ◽  
Norman L. Block ◽  
Gabor Halmos ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cell Lines ◽  
Renal Cell ◽  
Histological Evaluation ◽  
Growth Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Ghrh Receptor ◽  
Ghrh Antagonists

469 Background: Although targeted therapy has improved the clinical outcome for patients with metastatic renal cell carcinoma (RCC), a complete response is rare and therapy has adverse effects. Early antagonists of growth hormone-releasing hormone (GHRH) were shown to inhibit experimental RCC cell line, Caki-1, in vitro and in vivo. Herein, we investigate the effects of novel and highly potent antagonists of GHRH of MIA class on the growth of three RCC cell lines. Methods: The expression of GHRH receptor in all three cell lines was evaluated by ligand competition studies. The influence of GHRH antagonists MIA-602, MIA-604, MIA-606, and MIA-690 on cell viability was assessed by MTS assay in ACHN, A498, and 786-0 human RCC cells. GHRH antagonists were given at dose of 5µg daily in these three nude-mice xenograft models. Cell cycle parameters were analyzed by laser flow cytometry. Results: Ligand competition studies revealed specific, high affinity binding sites for GHRH receptor in all three RCC cell lines. GHRH antagonists inhibited the proliferation of all three RCC cells in a dose dependent manner. GHRH antagonists caused significant inhibition of tumor growth of ACHN, A498, and 786-0 RCCs ranged from 53-75% after 35 days of treatment (p<0.001). Treatment of ACHN cells with MIA-690 (10µM) led to a significant increase in number of cells with subG1DNA content, suggesting apoptosis. Conclusions: The effectiveness of the novel GHRH antagonists in inhibiting growth of experimental RCC models in vitro and in vivo was demonstrated. The inhibitory effect of GHRH antagonists is mainly due to direct inhibitory effects exerted through GHRH receptors. Biochemical and histological evaluation is needed to explore the mechanisms of action of GHRH antagonists in RCC.

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