Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model

John Chun Hao Chen, Hui Yen Chuang, Fei Ting Hsu, Yi Chen Chen, Yi Chun Chien, Jeng Jong Hwang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/ rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.

Original languageEnglish
Pages (from-to)85450-85463
Number of pages14
JournalOncotarget
Volume7
Issue number51
DOIs
Publication statusPublished - 2016
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinase Kinases
Hepatocellular Carcinoma
Radiotherapy
Appointments and Schedules
Therapeutics
Molecular Imaging
sorafenib
Extracellular Signal-Regulated MAP Kinases
Radio
Down-Regulation
Western Blotting
Radiation
Drug Therapy
Cell Line

Keywords

  • Hepatocellular carcinoma
  • MEK/ERK/NF-κB signaling
  • Molecular imaging
  • Radiation
  • Sorafenib

ASJC Scopus subject areas

  • Oncology

Cite this

Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model. / Chen, John Chun Hao; Chuang, Hui Yen; Hsu, Fei Ting; Chen, Yi Chen; Chien, Yi Chun; Hwang, Jeng Jong.

In: Oncotarget, Vol. 7, No. 51, 2016, p. 85450-85463.

Research output: Contribution to journalArticle

Chen, John Chun Hao ; Chuang, Hui Yen ; Hsu, Fei Ting ; Chen, Yi Chen ; Chien, Yi Chun ; Hwang, Jeng Jong. / Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model. In: Oncotarget. 2016 ; Vol. 7, No. 51. pp. 85450-85463.
@article{e598618828614866ba3e2e10f7c7c963,
title = "Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model",
abstract = "Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/ rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.",
keywords = "Hepatocellular carcinoma, MEK/ERK/NF-κB signaling, Molecular imaging, Radiation, Sorafenib",
author = "Chen, {John Chun Hao} and Chuang, {Hui Yen} and Hsu, {Fei Ting} and Chen, {Yi Chen} and Chien, {Yi Chun} and Hwang, {Jeng Jong}",
year = "2016",
doi = "10.18632/oncotarget.13398",
language = "English",
volume = "7",
pages = "85450--85463",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "51",

}

TY - JOUR

T1 - Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-κB pathway in human hepatocellular carcinoma-bearing mouse model

AU - Chen, John Chun Hao

AU - Chuang, Hui Yen

AU - Hsu, Fei Ting

AU - Chen, Yi Chen

AU - Chien, Yi Chun

AU - Hwang, Jeng Jong

PY - 2016

Y1 - 2016

N2 - Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/ rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.

AB - Patients with unresectable hepatocellular carcinoma (HCC) usually have poor prognosis because current monotherapy including surgery, chemotherapy and radiotherapy (RT) are not effective. Combination therapy may be effective to overcome this clinical problem. Here, we proposed the combination of sorafenib and RT, which have been applied in HCC treatment, could improve the treatment outcome of HCC. Our previous study showed that sorafenib could suppress the expression of NF-κB which is related to the chemo- and radio-resistance. Nevertheless, the expression of NF-κB is oscillatory and is affected by the treatments. Thus, understanding the oscillation of NF-κB expression would be beneficial for determining the optimal treatment schedule in combination therapy. Here established Huh7/NF-κB-tk-luc2/ rfp cell line, in which NF-κB indicates a NF-κB promoter, was utilized to noninvasively monitor the expression of NF-κB overtime in vitro and in vivo. The results show that pretreatment of sorafenib with RT suppresses the expressions of NF-κB and its downstream proteins induced by radiation through downregulation of phosphorylated extracellular signal-regulated kinase (pERK) most significantly compared with other treatment schedules. The results were further verified with Western blotting, EMSA, and NF-κB molecular imaging. These findings suggest that pretreatment of sorafenib with RT may be the ideal treatment schedule for the treatment of HCC.

KW - Hepatocellular carcinoma

KW - MEK/ERK/NF-κB signaling

KW - Molecular imaging

KW - Radiation

KW - Sorafenib

UR - http://www.scopus.com/inward/record.url?scp=85007463460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007463460&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.13398

DO - 10.18632/oncotarget.13398

M3 - Article

VL - 7

SP - 85450

EP - 85463

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 51

ER -