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KMID : 1034820230190020229
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Molecular & Cellular Toxicology
2023 Volume.19 No. 2 p.229 ~ p.236
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FoxM1 contributes to progestin resistance and epithelial-to-mesenchymal transition in endometrial carcinoma
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Lianhua Wang
Qiyang Shi
Shaorong Chen
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Abstract
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Background : Progestin resistance remains a major issue that is urgently needed to solve in progestin therapy for patients with endometrial carcinoma (EC). Increasing research indicated the critical role of FoxM1 in drug resistance of diverse cancers.
Objective : This study aims to explore whether FoxM1 contributes to medroxyprogesterone acetate (MPA, a commonly used progestin) resistance in EC.
Results : It was observed that FoxM1 is highly expressed in MPA-resistant ECC-1 (ECC-1/MPA) cells at both protein and mRNA levels when compared with ECC-1 cells. Knocking down FoxM1 in ECC-1/MPA cells significantly decreased the IC50 value of MPA, and rendered ECC-1/MPA cells more sensitive to MPA treatment. In vivo assay exhibited a similar tendency. Simultaneously, FoxM1 knockdown also suppressed proliferation, migration, and invasion of ECC-1/MPA cells. Furthermore, FoxM1 knockdown also suppressed epithelial-to-mesenchymal transition (EMT), as revealed by an elevation in E-cadherin expression and a decrease in N-cadherin and Vimentin expressions in ECC-1/MPA cells.
Conclusion : These findings indicated the role of FoxM1 in the MPA resistance of EC. Down-regulated FoxM1 expression might be a potential strategy for overcoming MPA resistance.
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KEYWORD
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Endometrial carcinoma, FoxM1, Progestin resistance, Epithelial-to-mesenchymal transition
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