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Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR
Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595284/ https://www.ncbi.nlm.nih.gov/pubmed/34805140 http://dx.doi.org/10.3389/fcell.2021.710721 |
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author | Yang, Yang Li, Jigang Yao, Lei Wu, Lile |
author_facet | Yang, Yang Li, Jigang Yao, Lei Wu, Lile |
author_sort | Yang, Yang |
collection | PubMed |
description | Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resistance. In the present study, we found that photodynamic therapy (PDT) treatment inhibited gemcitabine-resistant cholangiocarcinoma cells via repressing cell viability, enhancing cell apoptosis, and eliciting G1 cell cycle arrest through modulating Cyclin D1 and caspase 3 cleavage. In vivo, PDT treatment significantly inhibited the growth of gemcitabine-resistant cholangiocarcinoma cell-derived tumors. Online data mining and experimental analyses indicate that KLF10 expression was induced, whereas EGFR expression was downregulated by PDT treatment; KLF10 targeted the EGFR promoter region to inhibit EGFR transcription. Under PDT treatment, EGFR overexpression and KLF10 silencing attenuated the anti-cancer effects of PDT on gemcitabine-resistant cholangiocarcinoma cells by promoting cell viability, inhibiting apoptosis, and increasing S phase cell proportion. Importantly, under PDT treatment, the effects of KLF10 silencing were significantly reversed by EGFR silencing. In conclusion, PDT treatment induces KLF10 expression and downregulates EGFR expression. KLF10 binds to EGFR promoter region to inhibit EGFR transcription. The KLF10/EGFR axis participates in the process of the inhibition of PDT on gemcitabine-resistant cholangiocarcinoma cells. |
format | Online Article Text |
id | pubmed-8595284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85952842021-11-18 Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR Yang, Yang Li, Jigang Yao, Lei Wu, Lile Front Cell Dev Biol Cell and Developmental Biology Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resistance. In the present study, we found that photodynamic therapy (PDT) treatment inhibited gemcitabine-resistant cholangiocarcinoma cells via repressing cell viability, enhancing cell apoptosis, and eliciting G1 cell cycle arrest through modulating Cyclin D1 and caspase 3 cleavage. In vivo, PDT treatment significantly inhibited the growth of gemcitabine-resistant cholangiocarcinoma cell-derived tumors. Online data mining and experimental analyses indicate that KLF10 expression was induced, whereas EGFR expression was downregulated by PDT treatment; KLF10 targeted the EGFR promoter region to inhibit EGFR transcription. Under PDT treatment, EGFR overexpression and KLF10 silencing attenuated the anti-cancer effects of PDT on gemcitabine-resistant cholangiocarcinoma cells by promoting cell viability, inhibiting apoptosis, and increasing S phase cell proportion. Importantly, under PDT treatment, the effects of KLF10 silencing were significantly reversed by EGFR silencing. In conclusion, PDT treatment induces KLF10 expression and downregulates EGFR expression. KLF10 binds to EGFR promoter region to inhibit EGFR transcription. The KLF10/EGFR axis participates in the process of the inhibition of PDT on gemcitabine-resistant cholangiocarcinoma cells. Frontiers Media S.A. 2021-11-03 /pmc/articles/PMC8595284/ /pubmed/34805140 http://dx.doi.org/10.3389/fcell.2021.710721 Text en Copyright © 2021 Yang, Li, Yao and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Yang, Yang Li, Jigang Yao, Lei Wu, Lile Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title | Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title_full | Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title_fullStr | Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title_full_unstemmed | Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title_short | Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR |
title_sort | effect of photodynamic therapy on gemcitabine-resistant cholangiocarcinoma in vitro and in vivo through klf10 and egfr |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595284/ https://www.ncbi.nlm.nih.gov/pubmed/34805140 http://dx.doi.org/10.3389/fcell.2021.710721 |
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