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FoxM1 contributes to progestin resistance and epithelial-to-mesenchymal transition in endometrial carcinoma

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Abstract

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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Acknowledgements

The authors have no acknowledgements.

Funding

This work was supported by the Set sail Foundation of Fujian Medical University (2019QH1117).

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Authors and Affiliations

  1. Department of Gynecology, The Second Affiliated Hospital of Fujian Medical University, 950 Donghai Street, Fengze District, Quanzhou, Fujian, China

    Lianhua Wang, Qiyang Shi & Shaorong Chen

Authors
  1. Lianhua Wang
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  2. Qiyang Shi
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  3. Shaorong Chen
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Contributions

Conception or design of the work: LW; data collection: all the authors; data analysis and interpretation: all the authors; drafting the article: LW; critical revision of the article: QS and SC; final approval of the version to be published: all the authors.

Corresponding author

Correspondence to Lianhua Wang.

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Conflict of interest

Author Lianhua Wang declares that he/she has no conflict of interest. Author Qiyang Shi declares that he/she has no conflict of interest. Author Shaorong Chen declares that he/she has no conflict of interest.

Ethical approval

All procedures regarding animal were performed in accordance with the ethical standards as recommended by the International Committee of Medical Journal Editors and approved by the Medical Ethics Committee of the Second Affiliated Hospital of Fujian Medical University (Approved No. 416 [2020]).

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Supplementary Information

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13273_2022_251_MOESM1_ESM.tif

Supplementary Figure S1 (A) The transfection of sh-FoxM1#1 or sh-FoxM1#2 in ECC-1/MPA cells was observed under a fluorescence microscope. (B) On Day 7, the volume of xenografts from sh-NC and sh-FoxM1 cell-transplanted mice was record. After 7-day inoculation, saline were intraperitoneally injected into mice for 30 consecutive days. (C) The growth curve of xenograft volume from day 7 to day 37. (D) On the 37th day post-inoculation, mice were sacrificed, and xenografts were collected and weight. *p < 0.05 and **p < 0.01 compared with sh-NC (TIF 7566 kb)

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Wang, L., Shi, Q. & Chen, S. FoxM1 contributes to progestin resistance and epithelial-to-mesenchymal transition in endometrial carcinoma. Mol. Cell. Toxicol. 19, 229–236 (2023). https://doi.org/10.1007/s13273-022-00251-z

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  • DOI: https://doi.org/10.1007/s13273-022-00251-z

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