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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...

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Autores principales: Suh, Dong Hoon, Park, Wook Ha, Kim, Miseon, Kim, Kidong, No, Jae Hong, Kim, Yong Beom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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