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HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP
The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865712/ https://www.ncbi.nlm.nih.gov/pubmed/36674764 http://dx.doi.org/10.3390/ijms24021249 |
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author | Suh, Dong Hoon Park, Wook Ha Kim, Miseon Kim, Kidong No, Jae Hong Kim, Yong Beom |
author_facet | Suh, Dong Hoon Park, Wook Ha Kim, Miseon Kim, Kidong No, Jae Hong Kim, Yong Beom |
author_sort | Suh, Dong Hoon |
collection | PubMed |
description | The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2. |
format | Online Article Text |
id | pubmed-9865712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98657122023-01-22 HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP Suh, Dong Hoon Park, Wook Ha Kim, Miseon Kim, Kidong No, Jae Hong Kim, Yong Beom Int J Mol Sci Article The purpose of this study was to identify the role of HOXB9 and associated molecular mechanism in acquiring chemoresistance to ovarian cancer cells. After establishing HOXB9-overexpressing cells (HOXB9-OE/SKOV3), cisplatin resistance-induced cells (Cis-R/SKOV3), and an ovarian cancer xenograft mouse model, the effects of HOXB9 were evaluated in vitro and in vivo. Expression levels of ERCC-1, MRP-2, XIAP, and Bax/Bcl-2 were assessed as putative mechanisms mediating chemoresistance. Cisplatin-induced apoptosis was significantly decreased in HOXB9-OE/SKOV3 compared to SKOV3. Cisplatin treatment of SKOV3 strongly induced ERCC-1, MRP-2, and XIAP, and apoptosis was strongly induced through the inhibition of Bcl-2 and activation of Bax. ERCC-1, MRP-2, XIAP, and Bcl-2 were also strongly induced in HOXB9 OE/SKOV3. In contrast to SKOV3, cisplatin treatment alone of HOXB9 OE/SKOV3 did not affect the expression of Bcl-2 and Bax, and consequently, there was no increase in apoptosis. HOXB9 knockdown suppressed the expression of ERCC-1 and XIAP, but did not affect MRP-2 and Bcl-2/Bax expression in HOXB9 OE/SKOV3 and Cis-R/SKOV3, and caused a small increase in apoptosis. Treatment of SKOV3 with both cisplatin and siRNA_HOXB9 led to complete suppression of ERCC-1, MRP-2, and XIAP, and significantly increased apoptosis through inhibition of Bcl-2 expression and activation of Bax. The results observed in Cis-R/SKOV3 were similar to that in HOXB9 OE/SKOV3. Our data suggest that HOXB9 overexpression may cause chemoresistance in ovarian cancer cells by differential induction of ERCC-1, MRP-2, and XIAP depending on the strength of HOXB9 expression through inhibition of the mitochondrial pathway of apoptosis, including Bax/Bcl-2. MDPI 2023-01-08 /pmc/articles/PMC9865712/ /pubmed/36674764 http://dx.doi.org/10.3390/ijms24021249 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Suh, Dong Hoon Park, Wook Ha Kim, Miseon Kim, Kidong No, Jae Hong Kim, Yong Beom HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title | HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title_full | HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title_fullStr | HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title_full_unstemmed | HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title_short | HOXB9 Overexpression Confers Chemoresistance to Ovarian Cancer Cells by Inducing ERCC-1, MRP-2, and XIAP |
title_sort | hoxb9 overexpression confers chemoresistance to ovarian cancer cells by inducing ercc-1, mrp-2, and xiap |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865712/ https://www.ncbi.nlm.nih.gov/pubmed/36674764 http://dx.doi.org/10.3390/ijms24021249 |
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