Cargando…

Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model

Background: To investigate the efficacy of TACE combined with CQ, an autophagic inhibitor, in a rabbit VX2 liver tumor model. Methods: Tumor size was measured. And tumor growth rate was calculated to examine the effect of the combined treatment. Apoptosis was detected by TUNEL assay. Meanwhile, auto...

Descripción completa

Detalles Bibliográficos
Autores principales: Gao, Lu, Song, Jian-rui, Zhang, Jian-wei, Zhao, Xue, Zhao, Qiu-dong, Sun, Kai, Deng, Wei-jie, Li, Rong, Lv, Gang, Cheng, Hong-yan, Wei, Li-xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619094/
https://www.ncbi.nlm.nih.gov/pubmed/23569437
http://dx.doi.org/10.7150/ijbs.5925
_version_ 1782265464860180480
author Gao, Lu
Song, Jian-rui
Zhang, Jian-wei
Zhao, Xue
Zhao, Qiu-dong
Sun, Kai
Deng, Wei-jie
Li, Rong
Lv, Gang
Cheng, Hong-yan
Wei, Li-xin
author_facet Gao, Lu
Song, Jian-rui
Zhang, Jian-wei
Zhao, Xue
Zhao, Qiu-dong
Sun, Kai
Deng, Wei-jie
Li, Rong
Lv, Gang
Cheng, Hong-yan
Wei, Li-xin
author_sort Gao, Lu
collection PubMed
description Background: To investigate the efficacy of TACE combined with CQ, an autophagic inhibitor, in a rabbit VX2 liver tumor model. Methods: Tumor size was measured. And tumor growth rate was calculated to examine the effect of the combined treatment. Apoptosis was detected by TUNEL assay. Meanwhile, autophagic activity was detected by immunohistochemistry and Western blotting to investigate the mechanism underlying. Liver function was also examined to assess feasibility and safety of the combined therapy. Results: Tumors in the control grew more than 4 times bigger after 14 days, while that in the group of TACE alone just showed mild growth. But a slight shrinkage was shown after the treatment of CQ+TACE. Growth ratio of TACE alone was 96.45% ± 28.958% while that of CQ+TACE was -28.73% ± 12.265%. Compared with TACE alone, necrosis in CQ+TACE showed no significant difference, however, the apoptosis was much higher. There were only 14.8±3.11% apoptotic cells in TACE, but 33±4.18% in CQ+TACE, which suggests the increased apoptosis in CQ+TACE contributed to the decrease of tumor volume. In terms of autophagic activity, the result is negative when we immunostained sections of the control with LC3 antibody, but positive in TACE alone and CQ+TACE. And the result of Western blot showed that there was just a low level of LC3Ⅱexpressed in the control and CQ alone, but higher in TACE, and much higher in CQ+TACE because CQ inhibited its degradation in autophagy. Compared with control, p62 decreased in TACE, but the decrease was partially reversed in CQ+TACE. In addition, toxicity of CQ+TACE was assessed not higher than TACE alone, which supports the safety of CQ+TACE. Conclusion: CQ+TACE works better than TACE alone in rabbit VX2 liver tumor model because CQ inhibits autophagy induced by TACE. The inhibited autophagy loses its resistance to apoptosis that apoptosis increased, which contributes to the inhibition of tumor growth. This study indicates CQ may be a promising adjuvant to promote the effect of TACE.
format Online
Article
Text
id pubmed-3619094
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-36190942013-04-08 Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model Gao, Lu Song, Jian-rui Zhang, Jian-wei Zhao, Xue Zhao, Qiu-dong Sun, Kai Deng, Wei-jie Li, Rong Lv, Gang Cheng, Hong-yan Wei, Li-xin Int J Biol Sci Research Paper Background: To investigate the efficacy of TACE combined with CQ, an autophagic inhibitor, in a rabbit VX2 liver tumor model. Methods: Tumor size was measured. And tumor growth rate was calculated to examine the effect of the combined treatment. Apoptosis was detected by TUNEL assay. Meanwhile, autophagic activity was detected by immunohistochemistry and Western blotting to investigate the mechanism underlying. Liver function was also examined to assess feasibility and safety of the combined therapy. Results: Tumors in the control grew more than 4 times bigger after 14 days, while that in the group of TACE alone just showed mild growth. But a slight shrinkage was shown after the treatment of CQ+TACE. Growth ratio of TACE alone was 96.45% ± 28.958% while that of CQ+TACE was -28.73% ± 12.265%. Compared with TACE alone, necrosis in CQ+TACE showed no significant difference, however, the apoptosis was much higher. There were only 14.8±3.11% apoptotic cells in TACE, but 33±4.18% in CQ+TACE, which suggests the increased apoptosis in CQ+TACE contributed to the decrease of tumor volume. In terms of autophagic activity, the result is negative when we immunostained sections of the control with LC3 antibody, but positive in TACE alone and CQ+TACE. And the result of Western blot showed that there was just a low level of LC3Ⅱexpressed in the control and CQ alone, but higher in TACE, and much higher in CQ+TACE because CQ inhibited its degradation in autophagy. Compared with control, p62 decreased in TACE, but the decrease was partially reversed in CQ+TACE. In addition, toxicity of CQ+TACE was assessed not higher than TACE alone, which supports the safety of CQ+TACE. Conclusion: CQ+TACE works better than TACE alone in rabbit VX2 liver tumor model because CQ inhibits autophagy induced by TACE. The inhibited autophagy loses its resistance to apoptosis that apoptosis increased, which contributes to the inhibition of tumor growth. This study indicates CQ may be a promising adjuvant to promote the effect of TACE. Ivyspring International Publisher 2013-03-28 /pmc/articles/PMC3619094/ /pubmed/23569437 http://dx.doi.org/10.7150/ijbs.5925 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Research Paper
Gao, Lu
Song, Jian-rui
Zhang, Jian-wei
Zhao, Xue
Zhao, Qiu-dong
Sun, Kai
Deng, Wei-jie
Li, Rong
Lv, Gang
Cheng, Hong-yan
Wei, Li-xin
Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title_full Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title_fullStr Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title_full_unstemmed Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title_short Chloroquine Promotes the Anticancer Effect of TACE in a Rabbit VX2 Liver Tumor Model
title_sort chloroquine promotes the anticancer effect of tace in a rabbit vx2 liver tumor model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619094/
https://www.ncbi.nlm.nih.gov/pubmed/23569437
http://dx.doi.org/10.7150/ijbs.5925
work_keys_str_mv AT gaolu chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT songjianrui chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT zhangjianwei chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT zhaoxue chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT zhaoqiudong chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT sunkai chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT dengweijie chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT lirong chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT lvgang chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT chenghongyan chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel
AT weilixin chloroquinepromotestheanticancereffectoftaceinarabbitvx2livertumormodel