FOXM1 Promotes Drug Resistance in Cervical Cancer Cells by Regulating ABCC5 Gene Transcription

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2022 Feb 10

PMID 35141332

Authors

Youxiang Hou

Zhanfei Dong

Wei Zhong

Linglong Yin

Xiong Li

Gulina Kuerban

He Huang

Affiliations

Soon will be listed here.

Abstract

Objective: The aim of the present study was to investigate the effect of forkhead box M1 (FOXM1) to paclitaxel resistance in cervical cancer cells, to determine the underlying mechanism, and to identify novel targets for the treatment of paclitaxel-resistant cervical cancer.

Methods: Paclitaxel-resistant Caski cells (Caski/Taxol cells) were established by intermittently exposing the Caski cells to gradually increasing concentrations of paclitaxel. The association between FOXM1, ATP-binding cassette subfamily C member 5 (ABCC5), and cervical cancer cell drug resistance was assessed by overexpressing or knocking down the expression of FOXM1 in Caski or Caski/Taxol cells. The protein and mRNA expression levels, the ratio of cellular apoptosis, and cell migration as well as intracellular drug concentrations were measured in cells following the different treatments.

Results: After the successful establishment of resistant Caski/Taxol cells, cell cycle distribution analysis showed that a significantly larger percentage of Caski/Taxol cells was in the G0/G1 stage compared with the Caski cells ( < 0.01), whereas a significantly larger percentage of Caski cells was in the S and G2/M stage compared with the Caski/Taxol cells following treatment with paclitaxel ( < 0.01). Both the protein and mRNA expression levels of FOXM1 and ABCC5 transporters were significantly higher in the paclitaxel-resistant Caski/Taxol cells compared with Caski cells ( < 0.05). Knockdown of FOXM1 significantly lowered the protein expression levels of FOXM1 and ABCC5. Intracellular paclitaxel concentrations were significantly higher amongst the Caski/Taxol cells following the knockdown of FOXM1 by shRNA or Siomycin A ( < 0.05).

Conclusion: FOXM1 promotes drug resistance in cervical cancer cells by regulating ABCC5 gene transcription. The knockdown of FOXM1 with shRNA or Siomycin A promotes paclitaxel-induced cell death by regulating ABCC5 gene transcription.

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