Cargando…

Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells

Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroa...

Descripción completa

Detalles Bibliográficos
Autores principales: Yan, Xiao-Jing, Xie, Peng, Dai, Xu-Fang, Chen, Ling-Xi, Sun, Liang-Bo, Li, Tao, He, Wen-Hui, Xu, Zhi-Zhen, Huang, Gang, He, Feng-Tian, Lian, Ji-Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: OAE Publishing Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992565/
https://www.ncbi.nlm.nih.gov/pubmed/35582217
http://dx.doi.org/10.20517/cdr.2020.32
_version_ 1784683754850091008
author Yan, Xiao-Jing
Xie, Peng
Dai, Xu-Fang
Chen, Ling-Xi
Sun, Liang-Bo
Li, Tao
He, Wen-Hui
Xu, Zhi-Zhen
Huang, Gang
He, Feng-Tian
Lian, Ji-Qin
author_facet Yan, Xiao-Jing
Xie, Peng
Dai, Xu-Fang
Chen, Ling-Xi
Sun, Liang-Bo
Li, Tao
He, Wen-Hui
Xu, Zhi-Zhen
Huang, Gang
He, Feng-Tian
Lian, Ji-Qin
author_sort Yan, Xiao-Jing
collection PubMed
description Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroacetate (DCA) could enhance the sensitivity of liver cancer cells to pirarubicin (THP). Methods: Liver cancer cells were treated with DCA alone, THP alone, or DCA and THP combined. Cell viability was determined by the CCK-8 assay. Cell apoptosis was analyzed by flow cytometer. Reactive oxygen species (ROS) were detected using a CM-H2DCFDA fluorescence probe. Protein levels were identified by immunoblotting. Results: The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells. Changes in morphology and adherence ability were observed, as well as decreased cell viability. The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells. Moreover, compared with THP alone, combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells. The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation, cell viability and apoptosis. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was significantly increased in the DCA and THP combination group. The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125. Conclusion: The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway.
format Online
Article
Text
id pubmed-8992565
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher OAE Publishing Inc.
record_format MEDLINE/PubMed
spelling pubmed-89925652022-05-16 Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells Yan, Xiao-Jing Xie, Peng Dai, Xu-Fang Chen, Ling-Xi Sun, Liang-Bo Li, Tao He, Wen-Hui Xu, Zhi-Zhen Huang, Gang He, Feng-Tian Lian, Ji-Qin Cancer Drug Resist Original Article Aim: Liver cancer is one of the most common malignancies and has a high recurrence rate. However, current treatment strategies do not achieve satisfactory outcomes in the clinic. To explore a new strategy to enhance the effectiveness of chemotherapy in liver cancer, we investigated whether dichloroacetate (DCA) could enhance the sensitivity of liver cancer cells to pirarubicin (THP). Methods: Liver cancer cells were treated with DCA alone, THP alone, or DCA and THP combined. Cell viability was determined by the CCK-8 assay. Cell apoptosis was analyzed by flow cytometer. Reactive oxygen species (ROS) were detected using a CM-H2DCFDA fluorescence probe. Protein levels were identified by immunoblotting. Results: The results revealed that DCA significantly enhanced the antitumor effect of THP in liver cancer cells. Changes in morphology and adherence ability were observed, as well as decreased cell viability. The results of flow cytometry showed that the combination of THP and DCA significantly increased apoptosis of liver cancer cells. Moreover, compared with THP alone, combination treatment with DCA significantly increased THP-triggered ROS generation in liver cancer cells. The antioxidant N-acetyl-L-cysteine reversed the synergistic effect of DCA and THP on ROS generation, cell viability and apoptosis. Furthermore, phosphorylation of c-Jun N-terminal kinase (JNK) was significantly increased in the DCA and THP combination group. The effects of DCA and THP on cell viability and apoptosis were inhibited by the JNK inhibitor SP600125. Conclusion: The results obtained in the present study indicated that DCA enhanced the antitumor effect of THP in liver cancer cells via regulating the ROS-JNK signaling pathway. OAE Publishing Inc. 2020-09-04 /pmc/articles/PMC8992565/ /pubmed/35582217 http://dx.doi.org/10.20517/cdr.2020.32 Text en © The Author(s) 2020. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Yan, Xiao-Jing
Xie, Peng
Dai, Xu-Fang
Chen, Ling-Xi
Sun, Liang-Bo
Li, Tao
He, Wen-Hui
Xu, Zhi-Zhen
Huang, Gang
He, Feng-Tian
Lian, Ji-Qin
Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title_full Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title_fullStr Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title_full_unstemmed Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title_short Dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ROS-JNK signaling pathway in liver cancer cells
title_sort dichloroacetate enhances the antitumor effect of pirarubicin via regulating the ros-jnk signaling pathway in liver cancer cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8992565/
https://www.ncbi.nlm.nih.gov/pubmed/35582217
http://dx.doi.org/10.20517/cdr.2020.32
work_keys_str_mv AT yanxiaojing dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT xiepeng dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT daixufang dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT chenlingxi dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT sunliangbo dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT litao dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT hewenhui dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT xuzhizhen dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT huanggang dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT hefengtian dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells
AT lianjiqin dichloroacetateenhancestheantitumoreffectofpirarubicinviaregulatingtherosjnksignalingpathwayinlivercancercells