Combinatorial treatment with polyI

C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells

Wai Hoe Lau, Xiphias Ge Zhu, Shamaine Wei Ting Ho, Shu Chun Chang, Jeak-Ling Ding

研究成果: 雜誌貢獻 › 文章

3 引文 (Scopus)

摘要

Activation of TLR3 stimulates cancer cell apoptosis and triggers secretion of inflammatory cytokines. PolyI:C, a TLR3 agonist, activates immune cells and regresses metastatic lung cancer in vivo. Although polyI:C reportedly kills lung carcinomas, the mechanism remains elusive. Here, we demonstrated that polyI:C suppressed the proliferation and survival of metastatic (NCI-H358 and NCI-H292) and non-metastatic (A549) lung cancer cells. Notably, A549, NCI-H292 and NCI-H358 which are inducible by polyI:C, expressed low-to-medium level of TLR3 protein, and were susceptible to polyI:C treatment. By contrast, NCI-H1299, which endogenously expresses high level of TLR3 protein, was insensitive to polyI:C. We showed that polyI:C stimulated pro-inflammatory cytokines associated with survival and metastasis in a cell type-specific manner. While A549 and NCI-H292 released high levels of IL6, IL8 and GRO, the NCI-H358 cells endogenously secretes abundant levels of these cytokines, and was not further induced by polyI:C. Thus, NCI-H358 was resistant to the inhibition of cytokine-dependent metastasis. NCI-H1299, which was unresponsive to polyI:C, did not produce any of the pro-inflammatory cytokines. Treatment of A549 with a combination of polyI:C and anti-IL6 antibody significantly decreased IL6 production, and enhanced polyI:C-mediated killing and suppression of oncogenicity and metastasis. While polyI:C stimulated the phosphorylation of STAT3 and JAK2, blockade of these proteins enhanced polyI:C-mediated suppression of survival and metastasis. Taken together, polyI:C alone provoked apoptosis of lung cancer cells that express low-to-medium levels of functional TLR3 protein. The combinatorial treatment with polyI:C and anti-IL6 enhanced polyI:C-mediated anticancer activities through IL6/JAK2/STAT3 signalling, and apoptosis via TLR3-mediated caspase 3/8 pathway.
原文英語
頁（從 - 到）32884-32904
頁數21
期刊Oncotarget
卷8
發行號20
DOIs
出版狀態已發佈 - 2017

指紋

Interleukin-6
Lung Neoplasms
Apoptosis
Neoplasm Metastasis
Cytokines
Proteins
Caspase 8
Interleukin-8
Caspase 3
Anti-Idiotypic Antibodies
Phosphorylation
Carcinoma
Lung
Neoplasms

ASJC Scopus subject areas

  • Oncology

引用此文

Combinatorial treatment with polyI : C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells. / Lau, Wai Hoe; Zhu, Xiphias Ge; Ho, Shamaine Wei Ting; Chang, Shu Chun; Ding, Jeak-Ling.

於: Oncotarget, 卷 8, 編號 20, 2017, p. 32884-32904.

研究成果: 雜誌貢獻 › 文章

Lau, WH, Zhu, XG, Ho, SWT, Chang, SC & Ding, J-L 2017, 'Combinatorial treatment with polyI: C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells', Oncotarget, 卷 8, 編號 20, 頁 32884-32904. https://doi.org/10.18632/oncotarget.15862
Lau WH, Zhu XG, Ho SWT, Chang SC, Ding J-L. Combinatorial treatment with polyI: C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells. Oncotarget. 2017;8(20):32884-32904. https://doi.org/10.18632/oncotarget.15862
Lau, Wai Hoe ; Zhu, Xiphias Ge ; Ho, Shamaine Wei Ting ; Chang, Shu Chun ; Ding, Jeak-Ling. / Combinatorial treatment with polyI : C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells. 於: Oncotarget. 2017 ; 卷 8, 編號 20. 頁 32884-32904.
@article{3bd1101d6ebd4065804bc183b1ab548a,
title = "Combinatorial treatment with polyI: C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells",
abstract = "Activation of TLR3 stimulates cancer cell apoptosis and triggers secretion of inflammatory cytokines. PolyI:C, a TLR3 agonist, activates immune cells and regresses metastatic lung cancer in vivo. Although polyI:C reportedly kills lung carcinomas, the mechanism remains elusive. Here, we demonstrated that polyI:C suppressed the proliferation and survival of metastatic (NCI-H358 and NCI-H292) and non-metastatic (A549) lung cancer cells. Notably, A549, NCI-H292 and NCI-H358 which are inducible by polyI:C, expressed low-to-medium level of TLR3 protein, and were susceptible to polyI:C treatment. By contrast, NCI-H1299, which endogenously expresses high level of TLR3 protein, was insensitive to polyI:C. We showed that polyI:C stimulated pro-inflammatory cytokines associated with survival and metastasis in a cell type-specific manner. While A549 and NCI-H292 released high levels of IL6, IL8 and GRO, the NCI-H358 cells endogenously secretes abundant levels of these cytokines, and was not further induced by polyI:C. Thus, NCI-H358 was resistant to the inhibition of cytokine-dependent metastasis. NCI-H1299, which was unresponsive to polyI:C, did not produce any of the pro-inflammatory cytokines. Treatment of A549 with a combination of polyI:C and anti-IL6 antibody significantly decreased IL6 production, and enhanced polyI:C-mediated killing and suppression of oncogenicity and metastasis. While polyI:C stimulated the phosphorylation of STAT3 and JAK2, blockade of these proteins enhanced polyI:C-mediated suppression of survival and metastasis. Taken together, polyI:C alone provoked apoptosis of lung cancer cells that express low-to-medium levels of functional TLR3 protein. The combinatorial treatment with polyI:C and anti-IL6 enhanced polyI:C-mediated anticancer activities through IL6/JAK2/STAT3 signalling, and apoptosis via TLR3-mediated caspase 3/8 pathway.",
keywords = "Anti-IL6 antibody, Cytokines and caspase 3/7 apoptosis, JAK2/STAT3 antagonists, Lung cancer cells, polyI:C-TLR3 suppression of survival and metastasis",
author = "Lau, {Wai Hoe} and Zhu, {Xiphias Ge} and Ho, {Shamaine Wei Ting} and Chang, {Shu Chun} and Jeak-Ling Ding",
year = "2017",
doi = "10.18632/oncotarget.15862",
language = "English",
volume = "8",
pages = "32884--32904",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "20",

}

TY - JOUR

T1 - Combinatorial treatment with polyI

T2 - C and anti-IL6 enhances apoptosis and suppresses metastasis of lung cancer cells

AU - Lau, Wai Hoe

AU - Zhu, Xiphias Ge

AU - Ho, Shamaine Wei Ting

AU - Chang, Shu Chun

AU - Ding, Jeak-Ling

PY - 2017

Y1 - 2017

N2 - Activation of TLR3 stimulates cancer cell apoptosis and triggers secretion of inflammatory cytokines. PolyI:C, a TLR3 agonist, activates immune cells and regresses metastatic lung cancer in vivo. Although polyI:C reportedly kills lung carcinomas, the mechanism remains elusive. Here, we demonstrated that polyI:C suppressed the proliferation and survival of metastatic (NCI-H358 and NCI-H292) and non-metastatic (A549) lung cancer cells. Notably, A549, NCI-H292 and NCI-H358 which are inducible by polyI:C, expressed low-to-medium level of TLR3 protein, and were susceptible to polyI:C treatment. By contrast, NCI-H1299, which endogenously expresses high level of TLR3 protein, was insensitive to polyI:C. We showed that polyI:C stimulated pro-inflammatory cytokines associated with survival and metastasis in a cell type-specific manner. While A549 and NCI-H292 released high levels of IL6, IL8 and GRO, the NCI-H358 cells endogenously secretes abundant levels of these cytokines, and was not further induced by polyI:C. Thus, NCI-H358 was resistant to the inhibition of cytokine-dependent metastasis. NCI-H1299, which was unresponsive to polyI:C, did not produce any of the pro-inflammatory cytokines. Treatment of A549 with a combination of polyI:C and anti-IL6 antibody significantly decreased IL6 production, and enhanced polyI:C-mediated killing and suppression of oncogenicity and metastasis. While polyI:C stimulated the phosphorylation of STAT3 and JAK2, blockade of these proteins enhanced polyI:C-mediated suppression of survival and metastasis. Taken together, polyI:C alone provoked apoptosis of lung cancer cells that express low-to-medium levels of functional TLR3 protein. The combinatorial treatment with polyI:C and anti-IL6 enhanced polyI:C-mediated anticancer activities through IL6/JAK2/STAT3 signalling, and apoptosis via TLR3-mediated caspase 3/8 pathway.

AB - Activation of TLR3 stimulates cancer cell apoptosis and triggers secretion of inflammatory cytokines. PolyI:C, a TLR3 agonist, activates immune cells and regresses metastatic lung cancer in vivo. Although polyI:C reportedly kills lung carcinomas, the mechanism remains elusive. Here, we demonstrated that polyI:C suppressed the proliferation and survival of metastatic (NCI-H358 and NCI-H292) and non-metastatic (A549) lung cancer cells. Notably, A549, NCI-H292 and NCI-H358 which are inducible by polyI:C, expressed low-to-medium level of TLR3 protein, and were susceptible to polyI:C treatment. By contrast, NCI-H1299, which endogenously expresses high level of TLR3 protein, was insensitive to polyI:C. We showed that polyI:C stimulated pro-inflammatory cytokines associated with survival and metastasis in a cell type-specific manner. While A549 and NCI-H292 released high levels of IL6, IL8 and GRO, the NCI-H358 cells endogenously secretes abundant levels of these cytokines, and was not further induced by polyI:C. Thus, NCI-H358 was resistant to the inhibition of cytokine-dependent metastasis. NCI-H1299, which was unresponsive to polyI:C, did not produce any of the pro-inflammatory cytokines. Treatment of A549 with a combination of polyI:C and anti-IL6 antibody significantly decreased IL6 production, and enhanced polyI:C-mediated killing and suppression of oncogenicity and metastasis. While polyI:C stimulated the phosphorylation of STAT3 and JAK2, blockade of these proteins enhanced polyI:C-mediated suppression of survival and metastasis. Taken together, polyI:C alone provoked apoptosis of lung cancer cells that express low-to-medium levels of functional TLR3 protein. The combinatorial treatment with polyI:C and anti-IL6 enhanced polyI:C-mediated anticancer activities through IL6/JAK2/STAT3 signalling, and apoptosis via TLR3-mediated caspase 3/8 pathway.

KW - Anti-IL6 antibody

KW - Cytokines and caspase 3/7 apoptosis

KW - JAK2/STAT3 antagonists

KW - Lung cancer cells

KW - polyI:C-TLR3 suppression of survival and metastasis

UR - http://www.scopus.com/inward/record.url?scp=85019251984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019251984&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.15862

DO - 10.18632/oncotarget.15862

M3 - Article

VL - 8

SP - 32884

EP - 32904

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 20

ER -

存取文件