Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells

Abstract Background: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by...

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Autores principales:	Li,Qianwen, Zong,Yan, Li,Ke, Jie,Xiaohua, Hong,Jiaxin, Zhou,Xiaoshu, Wu,Bian, Li,Zhenyu, Zhang,Sheng, Wu,Gang, Meng,Rui
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2019
Materias:	Protein kinase CK2 Ionizing radiation Non-small cell lung cancer NF-κB Perivascular resistance niche (PVRN)
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100220
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spelling	oai:scielo:S0716-976020190001002202019-10-10Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cellsLi,QianwenZong,YanLi,KeJie,XiaohuaHong,JiaxinZhou,XiaoshuWu,BianLi,ZhenyuZhang,ShengWu,GangMeng,Rui Protein kinase CK2 Ionizing radiation Non-small cell lung cancer NF-κB Perivascular resistance niche (PVRN) Abstract Background: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by ionizing radiation (IR). Protein kinase CK2 is a constitutively active serine/threonine kinase which plays a vital role in cell proliferation and inflammation. In this study, we investigated the potential role of CK2 in PVRN after IR exposure. Result: Specific CK2 inhibitors, Quinalizarin and CX-4945, were employed to effectively suppressed the kinase activity of CK2 in human umbilical vein endothelial cells (HUVECs) without affecting their viability. Results showing that conditioned medium from IR-exposed HUVECs increased cell viability of A549 and H460 cells, and the pretreatment of CK2 inhibitors slowed down such increment. The secretion of IL-8 and IL-6 in HUVECs was induced after exposure with IR, but significantly inhibited by the addition of CK2 inhibitors. Furthermore, IR exposure elevated the nuclear phosphorylated factor-κB (NF-κB) p65 expression in HUVECs, which was a master factor regulating cytokine production. But when pretreated with CK2 inhibitors, such elevation was significantly suppressed. Conclusion: This study indicated that protein kinase CK2 is involved in the key process of the IR induced perivascular resistant niche, namely cytokine production, by endothelial cells, which finally led to radioresistance of non-small cell lung cancer cells. Thus, the inhibition of CK2 may be a promising way to improve the outcomes of radiation in nonsmall cell lung cancer cells.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100220en10.1186/s40659-019-0231-x
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Protein kinase CK2 Ionizing radiation Non-small cell lung cancer NF-κB Perivascular resistance niche (PVRN)
spellingShingle	Protein kinase CK2 Ionizing radiation Non-small cell lung cancer NF-κB Perivascular resistance niche (PVRN) Li,Qianwen Zong,Yan Li,Ke Jie,Xiaohua Hong,Jiaxin Zhou,Xiaoshu Wu,Bian Li,Zhenyu Zhang,Sheng Wu,Gang Meng,Rui Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
description	Abstract Background: Tumor microenvironment (TME) plays a vital role in determining the outcomes of radiotherapy. As an important component of TME, vascular endothelial cells are involved in the perivascular resistance niche (PVRN), which is formed by inflammation or cytokine production induced by ionizing radiation (IR). Protein kinase CK2 is a constitutively active serine/threonine kinase which plays a vital role in cell proliferation and inflammation. In this study, we investigated the potential role of CK2 in PVRN after IR exposure. Result: Specific CK2 inhibitors, Quinalizarin and CX-4945, were employed to effectively suppressed the kinase activity of CK2 in human umbilical vein endothelial cells (HUVECs) without affecting their viability. Results showing that conditioned medium from IR-exposed HUVECs increased cell viability of A549 and H460 cells, and the pretreatment of CK2 inhibitors slowed down such increment. The secretion of IL-8 and IL-6 in HUVECs was induced after exposure with IR, but significantly inhibited by the addition of CK2 inhibitors. Furthermore, IR exposure elevated the nuclear phosphorylated factor-κB (NF-κB) p65 expression in HUVECs, which was a master factor regulating cytokine production. But when pretreated with CK2 inhibitors, such elevation was significantly suppressed. Conclusion: This study indicated that protein kinase CK2 is involved in the key process of the IR induced perivascular resistant niche, namely cytokine production, by endothelial cells, which finally led to radioresistance of non-small cell lung cancer cells. Thus, the inhibition of CK2 may be a promising way to improve the outcomes of radiation in nonsmall cell lung cancer cells.
author	Li,Qianwen Zong,Yan Li,Ke Jie,Xiaohua Hong,Jiaxin Zhou,Xiaoshu Wu,Bian Li,Zhenyu Zhang,Sheng Wu,Gang Meng,Rui
author_facet	Li,Qianwen Zong,Yan Li,Ke Jie,Xiaohua Hong,Jiaxin Zhou,Xiaoshu Wu,Bian Li,Zhenyu Zhang,Sheng Wu,Gang Meng,Rui
author_sort	Li,Qianwen
title	Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
title_short	Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
title_full	Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
title_fullStr	Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
title_full_unstemmed	Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells
title_sort	involvement of endothelial ck2 in the radiation induced perivascular resistant niche (pvrn) and the induction of radioresistance for non-small cell lung cancer (nsclc) cells
publisher	Sociedad de Biología de Chile
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100220
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Involvement of endothelial CK2 in the radiation induced perivascular resistant niche (PVRN) and the induction of radioresistance for non-small cell lung cancer (NSCLC) cells

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