Cargando…

Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma

PURPOSE: Patients with hypopharyngeal carcinoma (HPC) often progress to an advanced clinical stage at diagnosis. Cisplatin has been widely used in first-line chemotherapy for advanced HPC. However, acquired chemotherapeutic resistance leads to recurrence, metastasis, and a poor survival rate. Theref...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Shiyu, Tan, Guolin, Wang, Tiansheng, Wang, Xianyao, Zhou, Zheng, Xiao, Jian, Li, Tieqi, Zhang, Gehou, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444389/
https://www.ncbi.nlm.nih.gov/pubmed/36072966
http://dx.doi.org/10.1155/2022/9341731
_version_ 1784783206208241664
author Zeng, Shiyu
Tan, Guolin
Wang, Tiansheng
Wang, Xianyao
Zhou, Zheng
Xiao, Jian
Li, Tieqi
Zhang, Gehou
Li, Wei
author_facet Zeng, Shiyu
Tan, Guolin
Wang, Tiansheng
Wang, Xianyao
Zhou, Zheng
Xiao, Jian
Li, Tieqi
Zhang, Gehou
Li, Wei
author_sort Zeng, Shiyu
collection PubMed
description PURPOSE: Patients with hypopharyngeal carcinoma (HPC) often progress to an advanced clinical stage at diagnosis. Cisplatin has been widely used in first-line chemotherapy for advanced HPC. However, acquired chemotherapeutic resistance leads to recurrence, metastasis, and a poor survival rate. Therefore, identifying new drug targets to improve treatment effects is still in need. METHODS: To screen the differential expression genes (DEGs) and proteins (DEPs), we conducted transcriptomic and proteomic analysis on cisplatin-sensitive cell lines (FaDu) and cisplatin-resistant cell lines (FaDu/DDP) of hypopharyngeal carcinoma. DEGs and DEPs, possibly the most associated with cisplatin-resistance, were verified by real-time polymerase chain reaction (RT-PCR) and western blot (WB), respectively, and the biological function of the screened S100A9 was further tested by CCK8, wound healing, and transwell assays. RESULTS: We identified S100A9 as a target for resensitizing the response to cisplatin in an acquired resistance model. S100A9 overexpression was significantly related to cisplatin resistance. Functional studies in vitro models demonstrated that downregulation of S100A9 overcame cisplatin-resistance and inhibited proliferation and migration. Later, we verified that downregulation of S100A9 suppressed the interleukin-6 (IL6) expression and epithelial-mesenchymal transition (EMT) pathway. CONCLUSION: In all, S100A9 plays a crucial role in cisplatin-resistance, proliferation, and migration of HPC. Targeting S100A9 may become a novel strategy for the treatment of HPC.
format Online
Article
Text
id pubmed-9444389
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-94443892022-09-06 Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma Zeng, Shiyu Tan, Guolin Wang, Tiansheng Wang, Xianyao Zhou, Zheng Xiao, Jian Li, Tieqi Zhang, Gehou Li, Wei J Oncol Research Article PURPOSE: Patients with hypopharyngeal carcinoma (HPC) often progress to an advanced clinical stage at diagnosis. Cisplatin has been widely used in first-line chemotherapy for advanced HPC. However, acquired chemotherapeutic resistance leads to recurrence, metastasis, and a poor survival rate. Therefore, identifying new drug targets to improve treatment effects is still in need. METHODS: To screen the differential expression genes (DEGs) and proteins (DEPs), we conducted transcriptomic and proteomic analysis on cisplatin-sensitive cell lines (FaDu) and cisplatin-resistant cell lines (FaDu/DDP) of hypopharyngeal carcinoma. DEGs and DEPs, possibly the most associated with cisplatin-resistance, were verified by real-time polymerase chain reaction (RT-PCR) and western blot (WB), respectively, and the biological function of the screened S100A9 was further tested by CCK8, wound healing, and transwell assays. RESULTS: We identified S100A9 as a target for resensitizing the response to cisplatin in an acquired resistance model. S100A9 overexpression was significantly related to cisplatin resistance. Functional studies in vitro models demonstrated that downregulation of S100A9 overcame cisplatin-resistance and inhibited proliferation and migration. Later, we verified that downregulation of S100A9 suppressed the interleukin-6 (IL6) expression and epithelial-mesenchymal transition (EMT) pathway. CONCLUSION: In all, S100A9 plays a crucial role in cisplatin-resistance, proliferation, and migration of HPC. Targeting S100A9 may become a novel strategy for the treatment of HPC. Hindawi 2022-08-29 /pmc/articles/PMC9444389/ /pubmed/36072966 http://dx.doi.org/10.1155/2022/9341731 Text en Copyright © 2022 Shiyu Zeng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zeng, Shiyu
Tan, Guolin
Wang, Tiansheng
Wang, Xianyao
Zhou, Zheng
Xiao, Jian
Li, Tieqi
Zhang, Gehou
Li, Wei
Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title_full Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title_fullStr Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title_full_unstemmed Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title_short Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma
title_sort downregulation of s100a9 reverses cisplatin-resistance and inhibits proliferation and migration in hypopharyngeal carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444389/
https://www.ncbi.nlm.nih.gov/pubmed/36072966
http://dx.doi.org/10.1155/2022/9341731
work_keys_str_mv AT zengshiyu downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT tanguolin downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT wangtiansheng downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT wangxianyao downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT zhouzheng downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT xiaojian downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT litieqi downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT zhanggehou downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma
AT liwei downregulationofs100a9reversescisplatinresistanceandinhibitsproliferationandmigrationinhypopharyngealcarcinoma