GW0742作为一种潜在的TRα和TRβ拮抗剂,可降低成人颗粒肿瘤细胞系的活力和代谢活性,并同时上调TRβ的表达。

IF 4.5 2区 医学 Q1 ONCOLOGY
Cancers Pub Date : 2024-12-05 DOI:10.3390/cancers16234069
Justyna Gogola-Mruk, Izabela Kumor, Gabriela Wojtaszek, Karolina Kulig, Anna Ptak
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引用次数: 0

摘要

本文章由计算机程序翻译,如有差异,请以英文原文为准。
GW0742 as a Potential TRα and TRβ Antagonist Reduces the Viability and Metabolic Activity of an Adult Granulosa Tumour Cell Line and Simultaneously Upregulates TRβ Expression.

Background/objectives: Clinical studies have demonstrated a correlation between alterations in the expression level of TRα and TRβ receptors in ovarian cancer cells and overall survival. Celecoxib and GW0742, commonly known as a COX-2 inhibitor and a PPARβ/δ agonist, are novel thyroid hormone receptor antagonists that bind to TRβ or both TRα and TRβ.

Methods: The study was conducted on a non-luteinized ovarian granulosa cell line (HGrC1) and two rare ovarian cancer cell lines (COV434 and KGN). The expression of TRα and TRβ at the gene and protein levels was examined by real-time PCR and Western blot, respectively. The impact of GW0742 and celecoxib on the cell viability of the HGrC1, COV434 and KGN lines was evaluated using the PrestoBlue™ Cell Viability Reagent. The metabolic activity of the cells was analysed using the Seahorse XFp Analyzer.

Results: Initially, we observed that the gene and protein expression levels of TRα and TRβ were higher in COV434 and KGN cells than in HGrC1 cells. Subsequently, it was demonstrated that T3 enhances the viability of HGrC1, COV434 and KGN cells. Furthermore, autoregulatory feedback loops were not observed during TRα or TRβ signalling in ovarian cancer cells, in contrast to the findings in healthy granulosa cells. Finally, we demonstrated that GW0742 reduced the viability and metabolic activity of granulosa cell tumours (GCTs). Simultaneously, we observed that GW0742 upregulated the expression of TRβ in GCT.

Conclusions: These findings suggest that GW0742 may be a novel adjuvant therapy for GCTs expressing TRα and TRβ.

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来源期刊
Cancers
Cancers Medicine-Oncology
CiteScore
8.00
自引率
9.60%
发文量
5371
审稿时长
18.07 days
期刊介绍: Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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