Low-dose 5-fluorouracil sensitizes HepG2 cells to TRAIL through TRAIL receptor DR5 and survivin-dependent mechanisms

Lijun Yang; Yutao Wang; Haifeng Zheng; Dong Zhang; Xiangwei Wu; Gongqin Sun; Tao Yang

doi:10.1080/1120009X.2016.1277048

Low-dose 5-fluorouracil sensitizes HepG2 cells to TRAIL through TRAIL receptor DR5 and survivin-dependent mechanisms

Lijun Yang, Yutao Wang, Haifeng Zheng, Dong Zhang, Xiangwei Wu, Gongqin Sun, Tao Yang

Clinical Cancer Prevention

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment due to its highly selective apoptosis-inducing action on tumour cells without harming normal cells. However, because of TRAIL resistance by some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In the present study, we investigated the sensitizing effect of 5-fluorouracil (5-FU) on TRAIL-induced apoptosis in TRAIL-resistant HepG2 hepatocarcinoma cells. The results show that 5-FU pretreatment could sensitize HepG2 cells to TRAIL-mediated apoptosis. The enhanced induction of cell death by the 5-FU/TRAIL combination was mediated by DR5 up-regulation and survivin down-regulation. Furthermore, this combination treatment significantly inhibited the growth of human xenografts in vivo. In conclusion, this study demonstrates that the combination of a sensitizing agent and TRAIL may be a novel and effective therapeutic regimen for treating human hepatocellular carcinoma.

Original language	English (US)
Pages (from-to)	179-188
Number of pages	10
Journal	Journal of Chemotherapy
Volume	29
Issue number	3
DOIs	https://doi.org/10.1080/1120009X.2016.1277048
State	Published - May 4 2017

Keywords

5-FU
Apoptosis
Chemotherapy
Hepatocarcinoma
TRAIL

ASJC Scopus subject areas

Oncology
Pharmacology
Pharmacology (medical)
Infectious Diseases

Access to Document

10.1080/1120009X.2016.1277048

Cite this

@article{173bbb8e813343779e8b744582a0b625,

title = "Low-dose 5-fluorouracil sensitizes HepG2 cells to TRAIL through TRAIL receptor DR5 and survivin-dependent mechanisms",

abstract = "Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment due to its highly selective apoptosis-inducing action on tumour cells without harming normal cells. However, because of TRAIL resistance by some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In the present study, we investigated the sensitizing effect of 5-fluorouracil (5-FU) on TRAIL-induced apoptosis in TRAIL-resistant HepG2 hepatocarcinoma cells. The results show that 5-FU pretreatment could sensitize HepG2 cells to TRAIL-mediated apoptosis. The enhanced induction of cell death by the 5-FU/TRAIL combination was mediated by DR5 up-regulation and survivin down-regulation. Furthermore, this combination treatment significantly inhibited the growth of human xenografts in vivo. In conclusion, this study demonstrates that the combination of a sensitizing agent and TRAIL may be a novel and effective therapeutic regimen for treating human hepatocellular carcinoma.",

keywords = "5-FU, Apoptosis, Chemotherapy, Hepatocarcinoma, TRAIL",

author = "Lijun Yang and Yutao Wang and Haifeng Zheng and Dong Zhang and Xiangwei Wu and Gongqin Sun and Tao Yang",

note = "Funding Information: This research was supported by grants from the National Natural Science Foundation of China [grant number 81101895], [grant number 81441021]; Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province [grant number 2014-779] and Research Project Supported by Shanxi Scholarship Council of China [grant number 2016-050]. We thank Prof. Paul Cohen from the University of Rhode Island for carefully proofreading the manuscript during revision. Publisher Copyright: {\textcopyright} 2017 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia (Italian Society of Chemotherapy).",

year = "2017",

month = may,

day = "4",

doi = "10.1080/1120009X.2016.1277048",

language = "English (US)",

volume = "29",

pages = "179--188",

journal = "Journal of Chemotherapy",

issn = "1120-009X",

publisher = "Maney Publishing",

number = "3",

}

TY - JOUR

T1 - Low-dose 5-fluorouracil sensitizes HepG2 cells to TRAIL through TRAIL receptor DR5 and survivin-dependent mechanisms

AU - Yang, Lijun

AU - Wang, Yutao

AU - Zheng, Haifeng

AU - Zhang, Dong

AU - Wu, Xiangwei

AU - Sun, Gongqin

AU - Yang, Tao

N1 - Funding Information: This research was supported by grants from the National Natural Science Foundation of China [grant number 81101895], [grant number 81441021]; Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province [grant number 2014-779] and Research Project Supported by Shanxi Scholarship Council of China [grant number 2016-050]. We thank Prof. Paul Cohen from the University of Rhode Island for carefully proofreading the manuscript during revision. Publisher Copyright: © 2017 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia (Italian Society of Chemotherapy).

PY - 2017/5/4

Y1 - 2017/5/4

N2 - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment due to its highly selective apoptosis-inducing action on tumour cells without harming normal cells. However, because of TRAIL resistance by some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In the present study, we investigated the sensitizing effect of 5-fluorouracil (5-FU) on TRAIL-induced apoptosis in TRAIL-resistant HepG2 hepatocarcinoma cells. The results show that 5-FU pretreatment could sensitize HepG2 cells to TRAIL-mediated apoptosis. The enhanced induction of cell death by the 5-FU/TRAIL combination was mediated by DR5 up-regulation and survivin down-regulation. Furthermore, this combination treatment significantly inhibited the growth of human xenografts in vivo. In conclusion, this study demonstrates that the combination of a sensitizing agent and TRAIL may be a novel and effective therapeutic regimen for treating human hepatocellular carcinoma.

AB - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment due to its highly selective apoptosis-inducing action on tumour cells without harming normal cells. However, because of TRAIL resistance by some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In the present study, we investigated the sensitizing effect of 5-fluorouracil (5-FU) on TRAIL-induced apoptosis in TRAIL-resistant HepG2 hepatocarcinoma cells. The results show that 5-FU pretreatment could sensitize HepG2 cells to TRAIL-mediated apoptosis. The enhanced induction of cell death by the 5-FU/TRAIL combination was mediated by DR5 up-regulation and survivin down-regulation. Furthermore, this combination treatment significantly inhibited the growth of human xenografts in vivo. In conclusion, this study demonstrates that the combination of a sensitizing agent and TRAIL may be a novel and effective therapeutic regimen for treating human hepatocellular carcinoma.

KW - 5-FU

KW - Apoptosis

KW - Chemotherapy

KW - Hepatocarcinoma

KW - TRAIL

UR - http://www.scopus.com/inward/record.url?scp=85008601948&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008601948&partnerID=8YFLogxK

U2 - 10.1080/1120009X.2016.1277048

DO - 10.1080/1120009X.2016.1277048

M3 - Article

C2 - 28067150

AN - SCOPUS:85008601948

SN - 1120-009X

VL - 29

SP - 179

EP - 188

JO - Journal of Chemotherapy

JF - Journal of Chemotherapy

IS - 3

ER -

Low-dose 5-fluorouracil sensitizes HepG2 cells to TRAIL through TRAIL receptor DR5 and survivin-dependent mechanisms

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this