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