Cargando…

Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway

Inflammatory bowel disease (IBD), characterized by sustained inflammation, is a latent risk factor of colon tumorigenesis. Silibinin has been reported to be anti-inflammatory and antineoplastic, but its efficacy on colitis-associated cancer (CAC) has not been reported. Interlukin-6/signal transducer...

Descripción completa

Detalles Bibliográficos
Autores principales: Zheng, Rongjuan, Ma, Jiaheng, Wang, Dan, Dong, Wenxiao, Wang, Sinan, Liu, Tianyu, Xie, Runxiang, Liu, Li, Wang, Bangmao, Cao, Hailong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222218/
https://www.ncbi.nlm.nih.gov/pubmed/30498394
http://dx.doi.org/10.1155/2018/1562010
_version_ 1783369157122719744
author Zheng, Rongjuan
Ma, Jiaheng
Wang, Dan
Dong, Wenxiao
Wang, Sinan
Liu, Tianyu
Xie, Runxiang
Liu, Li
Wang, Bangmao
Cao, Hailong
author_facet Zheng, Rongjuan
Ma, Jiaheng
Wang, Dan
Dong, Wenxiao
Wang, Sinan
Liu, Tianyu
Xie, Runxiang
Liu, Li
Wang, Bangmao
Cao, Hailong
author_sort Zheng, Rongjuan
collection PubMed
description Inflammatory bowel disease (IBD), characterized by sustained inflammation, is a latent risk factor of colon tumorigenesis. Silibinin has been reported to be anti-inflammatory and antineoplastic, but its efficacy on colitis-associated cancer (CAC) has not been reported. Interlukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) is the key signaling pathway involved in CAC. We evaluated the chemopreventive effect of silibinin on a CAC mouse model and determined its impact on IL-6/STAT3 signaling. Intestinal tumor cells (IMCE and HCT-116 cell lines) were also treated by graded concentration of silibinin, and cellular viability was determined. Silibinin (750 mg/kg/day) was administered to an azoxymethane/dextran sulfate sodium (AOM/DSS) C57BL/6 mouse model for 10 weeks by gavage. Body weight, colon length, and the amount and diameter of colon tumors were documented, respectively. Specimens were subjected to H&E staining for colitis and tumor scoring, immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick end labeling for proliferation assessment, and immunofluorescent staining for intestinal mucosa barrier assessment. Production of inflammatory cytokines was determined by real-time PCR. IL-6/STAT3 pathway activation was evaluated through immunohistochemical staining and western blot. In the current study, silibinin significantly inhibited the viability of intestinal tumor cells. The production of inflammatory cytokines and the phosphorylation of STAT3 were both inhibited in intestinal tumor cells. Meanwhile, silibinin decreased the amount and size of tumors in AOM/DSS mice. Colitis and tumor scores were decreased accompanying with inhibition of colonic tumor cell proliferation and promotion of cellular apoptosis. Additionally, silibinin could reduce the production of inflammatory cytokines and attenuate the impairment of colonic mucosal barrier. Furthermore, STAT3 phosphorylation was significantly suppressed by silibinin. In conclusion, silibinin could protect against colitis-associated tumorigenesis in mice via inhibiting IL-6/STAT3, which showed promising chemopreventive potential of CAC.
format Online
Article
Text
id pubmed-6222218
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-62222182018-11-29 Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway Zheng, Rongjuan Ma, Jiaheng Wang, Dan Dong, Wenxiao Wang, Sinan Liu, Tianyu Xie, Runxiang Liu, Li Wang, Bangmao Cao, Hailong Mediators Inflamm Research Article Inflammatory bowel disease (IBD), characterized by sustained inflammation, is a latent risk factor of colon tumorigenesis. Silibinin has been reported to be anti-inflammatory and antineoplastic, but its efficacy on colitis-associated cancer (CAC) has not been reported. Interlukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) is the key signaling pathway involved in CAC. We evaluated the chemopreventive effect of silibinin on a CAC mouse model and determined its impact on IL-6/STAT3 signaling. Intestinal tumor cells (IMCE and HCT-116 cell lines) were also treated by graded concentration of silibinin, and cellular viability was determined. Silibinin (750 mg/kg/day) was administered to an azoxymethane/dextran sulfate sodium (AOM/DSS) C57BL/6 mouse model for 10 weeks by gavage. Body weight, colon length, and the amount and diameter of colon tumors were documented, respectively. Specimens were subjected to H&E staining for colitis and tumor scoring, immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick end labeling for proliferation assessment, and immunofluorescent staining for intestinal mucosa barrier assessment. Production of inflammatory cytokines was determined by real-time PCR. IL-6/STAT3 pathway activation was evaluated through immunohistochemical staining and western blot. In the current study, silibinin significantly inhibited the viability of intestinal tumor cells. The production of inflammatory cytokines and the phosphorylation of STAT3 were both inhibited in intestinal tumor cells. Meanwhile, silibinin decreased the amount and size of tumors in AOM/DSS mice. Colitis and tumor scores were decreased accompanying with inhibition of colonic tumor cell proliferation and promotion of cellular apoptosis. Additionally, silibinin could reduce the production of inflammatory cytokines and attenuate the impairment of colonic mucosal barrier. Furthermore, STAT3 phosphorylation was significantly suppressed by silibinin. In conclusion, silibinin could protect against colitis-associated tumorigenesis in mice via inhibiting IL-6/STAT3, which showed promising chemopreventive potential of CAC. Hindawi 2018-10-25 /pmc/articles/PMC6222218/ /pubmed/30498394 http://dx.doi.org/10.1155/2018/1562010 Text en Copyright © 2018 Rongjuan Zheng et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zheng, Rongjuan
Ma, Jiaheng
Wang, Dan
Dong, Wenxiao
Wang, Sinan
Liu, Tianyu
Xie, Runxiang
Liu, Li
Wang, Bangmao
Cao, Hailong
Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title_full Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title_fullStr Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title_full_unstemmed Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title_short Chemopreventive Effects of Silibinin on Colitis-Associated Tumorigenesis by Inhibiting IL-6/STAT3 Signaling Pathway
title_sort chemopreventive effects of silibinin on colitis-associated tumorigenesis by inhibiting il-6/stat3 signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222218/
https://www.ncbi.nlm.nih.gov/pubmed/30498394
http://dx.doi.org/10.1155/2018/1562010
work_keys_str_mv AT zhengrongjuan chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT majiaheng chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT wangdan chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT dongwenxiao chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT wangsinan chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT liutianyu chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT xierunxiang chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT liuli chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT wangbangmao chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway
AT caohailong chemopreventiveeffectsofsilibininoncolitisassociatedtumorigenesisbyinhibitingil6stat3signalingpathway