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Canagliflozin ameliorates progestin resistance by suppressing RARβ/CRABP2 signaling in TRβ knockout endometrial cancer cells

ABSTRACT: THRB-knockout RL95-2 (THRB(-/-)/RL95-2) cells were constructed to investigate progestin resistance mechanisms. Cell proliferation and apoptosis were assessed in RL95-2 and THRB(-/-)/RL95-2 cells treated with canagliflozin (CANA), medroxyprogesterone acetate (MPA), or their combination using CCK-8, EdU, and flow cytometry assays. In vivo, nude mouse xenograft models were used to evaluate CANA and MPA efficacy. Transcriptomic and proteomic analyses identified pathways associated with progestin resistance. Molecular dynamics simulations, western blotting, and immunohistochemistry identified CANA targets. Electrophoretic mobility shift assays and dual luciferase reporter assays evaluated the regulatory effects of TRβ, RARβ, and CRABP2.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yan Zhu

PROVIDER: PXD060591 | iProX | Fri Feb 07 00:00:00 GMT 2025

REPOSITORIES: iProX

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Canagliflozin alleviates progestin resistance by suppressing RARβ/CRABP2 signaling in THRB knockout endometrial cancer cells.

Yang Ye Y Zhou Jieyun J Lv Qiaoying Q Ni Qicheng Q Hu Baichun B Wang Yulong Y Qu Shuning S Li Guoting G Yang Wenjie W Zhong Ruihua R Chen Xiaojun X Zhu Yan Y

Frontiers in pharmacology 20250430

<h4>Introduction</h4>Progestin resistance has emerged as a significant barrier to the conservative management of endometrial cancer (EC). The mechanisms underlying progestin resistance in endocrine therapy remain incompletely understood. Previous studies have suggested that silencing thyroid hormone receptor B (THRB) is associated with progestin resistance in EC cells.<h4>Methods</h4>THRB-knockout RL95-2 (THRB<sup>(-/-)</sup>/RL95-2) cells were constructed to investigate progestin resistance mec ...[more]

PMID: 40371351

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