Cargando…

Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells

PURPOSE: To determine the exact effect of Interleukin-6 (IL-6) on tumor cell proliferation, apoptosis, invasion, and anti-cancer therapy in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: IL-6 was disrupted by transcription activator-like effector nucleases (TALEN) in HCCLM3 cells, and was used...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhuang, Peng-Yuan, Zhang, Ke-Wei, Wang, Jian-Dong, Zhou, Xue-Ping, Liu, Ying-Bin, Quan, Zhi-Wei, Shen, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652824/
https://www.ncbi.nlm.nih.gov/pubmed/29100435
http://dx.doi.org/10.18632/oncotarget.20946
_version_ 1783273137342775296
author Zhuang, Peng-Yuan
Zhang, Ke-Wei
Wang, Jian-Dong
Zhou, Xue-Ping
Liu, Ying-Bin
Quan, Zhi-Wei
Shen, Jun
author_facet Zhuang, Peng-Yuan
Zhang, Ke-Wei
Wang, Jian-Dong
Zhou, Xue-Ping
Liu, Ying-Bin
Quan, Zhi-Wei
Shen, Jun
author_sort Zhuang, Peng-Yuan
collection PubMed
description PURPOSE: To determine the exact effect of Interleukin-6 (IL-6) on tumor cell proliferation, apoptosis, invasion, and anti-cancer therapy in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: IL-6 was disrupted by transcription activator-like effector nucleases (TALEN) in HCCLM3 cells, and was used to evaluate the role of IL-6 on tumor cell proliferation, apoptosis, invasion and key signaling pathways involved in sorafenib and/or IFNα therapy. RESULTS: IL-6 has no direct effect on cell proliferation and invasion but promotes cell apoptosis and up-regulate IL-33 and VEGF-A expression. IL-6 could attenuate the anti-proliferation effect by sorafenib and combination therapy but facilitate the pro-apoptosis of the combination therapy and augment the pro-invasive effect induced by single treatment. IL-6 could down-regulate p-STAT3, however up-regulate the p-MEK/p-ERK and NF-kB/iNOS expression, and it also facilitated the promotion on p-JAK2 and p-MEK/p-ERK by either sorafenib or IFN-α. in vivo study, IL-6 significantly promotes tumor growth. The combination treatment showed the highest inhibition on tumor growth which is derived from HCCLM3-IL6(-) cells. CONCLUSIONS: IL-6 has no direct effect on cell proliferation and invasion but promotes tumor cell apoptosis in vitro study. Sorafenib and combination therapies are suitable for HCC cells with low or no IL-6 expression confirmed in vivo study.
format Online
Article
Text
id pubmed-5652824
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-56528242017-11-02 Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells Zhuang, Peng-Yuan Zhang, Ke-Wei Wang, Jian-Dong Zhou, Xue-Ping Liu, Ying-Bin Quan, Zhi-Wei Shen, Jun Oncotarget Research Paper PURPOSE: To determine the exact effect of Interleukin-6 (IL-6) on tumor cell proliferation, apoptosis, invasion, and anti-cancer therapy in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: IL-6 was disrupted by transcription activator-like effector nucleases (TALEN) in HCCLM3 cells, and was used to evaluate the role of IL-6 on tumor cell proliferation, apoptosis, invasion and key signaling pathways involved in sorafenib and/or IFNα therapy. RESULTS: IL-6 has no direct effect on cell proliferation and invasion but promotes cell apoptosis and up-regulate IL-33 and VEGF-A expression. IL-6 could attenuate the anti-proliferation effect by sorafenib and combination therapy but facilitate the pro-apoptosis of the combination therapy and augment the pro-invasive effect induced by single treatment. IL-6 could down-regulate p-STAT3, however up-regulate the p-MEK/p-ERK and NF-kB/iNOS expression, and it also facilitated the promotion on p-JAK2 and p-MEK/p-ERK by either sorafenib or IFN-α. in vivo study, IL-6 significantly promotes tumor growth. The combination treatment showed the highest inhibition on tumor growth which is derived from HCCLM3-IL6(-) cells. CONCLUSIONS: IL-6 has no direct effect on cell proliferation and invasion but promotes tumor cell apoptosis in vitro study. Sorafenib and combination therapies are suitable for HCC cells with low or no IL-6 expression confirmed in vivo study. Impact Journals LLC 2017-09-15 /pmc/articles/PMC5652824/ /pubmed/29100435 http://dx.doi.org/10.18632/oncotarget.20946 Text en Copyright: © 2017 Zhuang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhuang, Peng-Yuan
Zhang, Ke-Wei
Wang, Jian-Dong
Zhou, Xue-Ping
Liu, Ying-Bin
Quan, Zhi-Wei
Shen, Jun
Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title_full Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title_fullStr Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title_full_unstemmed Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title_short Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells
title_sort effect of talen-mediated il-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (hcc-lm3) cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652824/
https://www.ncbi.nlm.nih.gov/pubmed/29100435
http://dx.doi.org/10.18632/oncotarget.20946
work_keys_str_mv AT zhuangpengyuan effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT zhangkewei effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT wangjiandong effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT zhouxueping effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT liuyingbin effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT quanzhiwei effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells
AT shenjun effectoftalenmediatedil6knockoutoncellproliferationapoptosisinvasionandanticancertherapyinhepatocellularcarcinomahcclm3cells