Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Park, Young Ae; Choi, Chel Hun; Gu, In; Song, Sang Yong; Lee, Jae Kwan; Cho, Young Jae; Choi, Ji Yoon; Jeon, Hye Kyung; Ryu, Ji Yoon; Lee, Yoo-Young; Kim, Tae Joong; Bae, Duk Soo; Lee, Jeong Won

doi:10.1016/j.ygyno.2014.06.031

Cited by 32 publications

(26 citation statements)

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“…For example, inhibition of the AGTR1 expression in human epithelial ovarian carcinomas reduces cell survival and angiogenesis by repressing the level of VEGF [37]. AGTR1 is also involved in the invasion, migration or tumorigenesis of endometrial carcinoma and breast cancer via the up-regulation of VEGF [38–40].…”

Section: Discussionmentioning

confidence: 99%

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

Zhao

Hou

et al. 2017

BMC Cancer

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BackgroundChemoresistance hinders the curative cancer chemotherapy. MicroRNAs (miRNAs) are key players in diverse biological processes including the chemoresistance of cancers.MethodsA RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells was performed to detect the levels of miR-34a-5p. Bioinformatics analysis revealed that AGTR1 is one of the target genes of miR-34a-5p. The mRNA and protein levels of AGTR1 were detected in both the miR-34a-5p-mimic transfected G-292 and miR-34a-5p-antagomiR transfected SJSA-1 cells. The involvement of AGTR1 with OS chemoresistance was validated by the experiments with siRNA-mediated repression or overexpression of the AGTR1 gene.ResultsWe showed that miR-34a-5p promotes the multi- chemoresistance of OS. The angiotensin II type 1 receptor (AGTR1) gene, is one of the targets of miR-34a-5p in OS and thus negatively correlates with OS chemoresistance by systematic investigations of a multi-drug sensitive (G-292) and resistant (SJSA-1) OS cell lines. Down-regulation of the AGTR1 expression by siRNA passivates G-292 cells and suppresses cell apoptosis, while over-expression of AGTR1 sensitizes SJSA-1 cells and thus promotes the drug-triggered cell death.ConclusionsThe miR-34a-5p and its target gene AGTR1 are the potential targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3002-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

Zhao

Hou

et al. 2017

BMC Cancer

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“…Therefore, AGTR1 antagonists might be useful for suppressing tumor angiogenesis in ovarian cancer. Targeting AGTR1 could significantly inhibit tumor growth via inactivation of the phosphorylation of PLC β3, which could disrupt tumor angiogenesis by reducing the VEGF production, thus inhibiting endothelial cell survival (72). However, the source of the VEGF secretion (either endothelial cells or ovarian cancer cells) and the molecular mechanism responsible for angiotensin II-mediated endothelial cell migration and microvessel formation remain unknown.…”

Section: Angiotensin II Type 1 Receptormentioning

confidence: 99%

The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

et al. 2017

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Ovarian cancer is the seventh most common cancer in women and the most lethal gynecological cancer, causing over 151,000 deaths worldwide each year. Dysregulated production of endocrine hormones, known to have pluripotent effects on cell function through the activation of receptor signaling pathways, is believed to be a high-risk factor for ovarian cancer. An increasing body of evidence suggests that endocrine G protein-coupled receptors (GPCRs) are involved in the progression and metastasis of ovarian neoplasms. GPCRs are attractive drug targets because their activities are regulated by more than 25% of all drugs approved by the Food and Drug Administration. Therefore, understanding the role of endocrine GPCRs during ovarian cancer progression and metastasis will allow for the development of novel strategies to design effective chemotherapeutic drugs against malignant ovarian tumors. In this review, we address the signaling pathways and functional roles of several key endocrine GPCRs that are related to the cause, progression, and metastasis of ovarian cancer.

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“…Another area of potential therapeutic benefit of AT2R agonists such as 8 is cancer. Notably, regarding cancer and based on experiments with 8 or an AT2R selective peptide agonist, it was proposed that AT2R agonists might find a therapeutic role in the treatment of pancreatic ductal adenocarcinoma, prostate cancer, lung cancer, hepatocellular carcinoma, epithelial ovarian carcinoma, colorectal carcinoma, uterine leiomyosarcoma, and Lewis lung carcinoma …”

Section: Introductionmentioning

confidence: 99%

Small‐molecule AT2 receptor agonists

Hallberg

Sumners

Steckelings

et al. 2017

Medicinal Research Reviews

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The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist with the highest affinity for the AT2R reported to date (K = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also presented.

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Dual targeting of angiotensin receptors (AGTR1 and AGTR2) in epithelial ovarian carcinoma

Cited by 32 publications

References 31 publications

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene

The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

Small‐molecule AT2 receptor agonists

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