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Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression
BACKGROUND: The drug resistance of chemotherapeutic agents leads to unsatisfactory survival rates for cervical cancer (CC) patients. We aimed to explore the effect of FOXP2 on the sensitivity of CC cells to cisplatin (DDP) and its mechanism in Changde, China in 2018. METHODS: A Total of 6 cervical c...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Tehran University of Medical Sciences
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430408/ https://www.ncbi.nlm.nih.gov/pubmed/37593506 http://dx.doi.org/10.18502/ijph.v52i7.13249 |
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author | Chen, Ziqin Xiao, Zemin Tian, Wei Li, Zongjuan Wu, Tao |
author_facet | Chen, Ziqin Xiao, Zemin Tian, Wei Li, Zongjuan Wu, Tao |
author_sort | Chen, Ziqin |
collection | PubMed |
description | BACKGROUND: The drug resistance of chemotherapeutic agents leads to unsatisfactory survival rates for cervical cancer (CC) patients. We aimed to explore the effect of FOXP2 on the sensitivity of CC cells to cisplatin (DDP) and its mechanism in Changde, China in 2018. METHODS: A Total of 6 cervical cancer tissue samples including 3 patients with cisplatin sensitivity and 3 patients with cisplatin resistance, who received DDP-based treatment, were obtained from Changde First People's Hospital, Changde City during 2021, and FOXP2 level was detected by Western blot. The expression levels of FOXP2 and c-MET (hepatocyte growth factor receptor, c-MET) in cells were determined by q-PCR and Western blot analysis. The cell survival, apoptosis, and clone formation were analyzed by flow cytometry, MTT assay, or clone formation assay. Dual-luciferase reporter assays and Chromatin immunoprecipitation were applied to verify the regulation between FOXP2 and c-MET. RESULTS: FOXP2 was downregulated in cisplatin-resistant cervical cancer tissues and cells compared with control. FOXP2 overexpression in SiHa/DDP cells inhibited cell proliferation and promoted cell apoptosis, whereas down-regulation of FOXP2 in SiHa cells had the opposite result. FOXP2 enhanced chemosensitive to DDP in CC cells. FOXP2 is negatively correlated with c-MET expression level in SiHa and SiHa/DDP cells. Mechanistically, FOXP2 binds to the promoter region of c-MET to regulate its expression in CC cells negatively. Overexpression of c-MET can attenuate the enhancement of DDP-induced apoptosis caused by FOXP2 overexpression. CONCLUSION: This is a novel study on the role of FOXP2 in promoting the DDP sensitivity of CC cells by inhibiting c-MET. The FOXP2/c-MET signaling axis uncovered in the present study may be a novel therapeutic target for the DDP therapy resistance of CC. |
format | Online Article Text |
id | pubmed-10430408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Tehran University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-104304082023-08-17 Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression Chen, Ziqin Xiao, Zemin Tian, Wei Li, Zongjuan Wu, Tao Iran J Public Health Original Article BACKGROUND: The drug resistance of chemotherapeutic agents leads to unsatisfactory survival rates for cervical cancer (CC) patients. We aimed to explore the effect of FOXP2 on the sensitivity of CC cells to cisplatin (DDP) and its mechanism in Changde, China in 2018. METHODS: A Total of 6 cervical cancer tissue samples including 3 patients with cisplatin sensitivity and 3 patients with cisplatin resistance, who received DDP-based treatment, were obtained from Changde First People's Hospital, Changde City during 2021, and FOXP2 level was detected by Western blot. The expression levels of FOXP2 and c-MET (hepatocyte growth factor receptor, c-MET) in cells were determined by q-PCR and Western blot analysis. The cell survival, apoptosis, and clone formation were analyzed by flow cytometry, MTT assay, or clone formation assay. Dual-luciferase reporter assays and Chromatin immunoprecipitation were applied to verify the regulation between FOXP2 and c-MET. RESULTS: FOXP2 was downregulated in cisplatin-resistant cervical cancer tissues and cells compared with control. FOXP2 overexpression in SiHa/DDP cells inhibited cell proliferation and promoted cell apoptosis, whereas down-regulation of FOXP2 in SiHa cells had the opposite result. FOXP2 enhanced chemosensitive to DDP in CC cells. FOXP2 is negatively correlated with c-MET expression level in SiHa and SiHa/DDP cells. Mechanistically, FOXP2 binds to the promoter region of c-MET to regulate its expression in CC cells negatively. Overexpression of c-MET can attenuate the enhancement of DDP-induced apoptosis caused by FOXP2 overexpression. CONCLUSION: This is a novel study on the role of FOXP2 in promoting the DDP sensitivity of CC cells by inhibiting c-MET. The FOXP2/c-MET signaling axis uncovered in the present study may be a novel therapeutic target for the DDP therapy resistance of CC. Tehran University of Medical Sciences 2023-07 /pmc/articles/PMC10430408/ /pubmed/37593506 http://dx.doi.org/10.18502/ijph.v52i7.13249 Text en Copyright © 2023 Chen et al. Published by Tehran University of Medical Sciences. https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International license (https://creativecommons.org/licenses/by-nc/4.0/). Non-commercial uses of the work are permitted, provided the original work is properly cited. |
spellingShingle | Original Article Chen, Ziqin Xiao, Zemin Tian, Wei Li, Zongjuan Wu, Tao Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title | Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title_full | Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title_fullStr | Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title_full_unstemmed | Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title_short | Two Enhances the Cisplatin Sensitivity of Cervical Cancer Cells via Suppression of c-MET Expression |
title_sort | two enhances the cisplatin sensitivity of cervical cancer cells via suppression of c-met expression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430408/ https://www.ncbi.nlm.nih.gov/pubmed/37593506 http://dx.doi.org/10.18502/ijph.v52i7.13249 |
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