Cargando…

Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride

Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study,...

Descripción completa

Detalles Bibliográficos
Autores principales: Shen, Conghuan, Li, Jianhua, Li, Ruidong, Ma, Zhenyu, Tao, Yifeng, Zhang, Quanbao, Wang, Zhengxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289293/
https://www.ncbi.nlm.nih.gov/pubmed/35860597
http://dx.doi.org/10.3389/fonc.2022.901705
_version_ 1784748633534496768
author Shen, Conghuan
Li, Jianhua
Li, Ruidong
Ma, Zhenyu
Tao, Yifeng
Zhang, Quanbao
Wang, Zhengxin
author_facet Shen, Conghuan
Li, Jianhua
Li, Ruidong
Ma, Zhenyu
Tao, Yifeng
Zhang, Quanbao
Wang, Zhengxin
author_sort Shen, Conghuan
collection PubMed
description Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study, we demonstrated the mechanism of tumor-derived DNA on the CXCL12-CXCR4 and CCL21-CCR7 axes of hepatocellular carcinoma (HCC) cells and the regulatory effect of sinomenine hydrochloride. Tumor-derived DNA was separated from HCCLM cell lines. Tumor-derived DNA was transfected into SK-Hep1 cells by Lipofectamine 2000. We found that sinomenine hydrochloride reduced the expression of CXCR4, CXCR12, CCR7, and CCL21 in HCC cells, suppressed the growth and invasion of HCC cells, and increased apoptosis. In contrast to the controls, the protein expressions of CXCR4, CXCL12, CCR7, CCL21, P-ERK1/2, MMP-9, and MMP-2 in SK-Hep1 cells were significantly increased after transfection of tumor-derived DNA, while the increase was reversed by sinobine hydrochloride. Acid sinomenine interferes with tumor-derived DNA and affects ERK/MMP signaling via the CXCL12/CXCR4 axis in HCC cells. CXCR4 siRNA and CCR7 siRNA attenuated tumor-derived DNA activation of ERK1/2/MMP2/9 signaling pathways in HCC cells. CXCR4-oe and CCR7-OE enhance the stimulation of erK1/2/MMP2/9 signaling pathway by tumor-derived DNA in HCC cells. Tumor-derived DNA reduced apoptosis and increased invasion of SK-Hep1 cells by CXCL12-CXCR4 axis and CCL21-CCR7 axis, and sinobine hydrochloride reversed this regulation. These results strongly suggest that tumor-derived DNA can increase the growth and invasion of oncocytes via the upregulation of the expression of CXCL12-CXCR4 and CCL21-CCR7 axis and through ERK1/2/MMP2/9 signaling pathway in HCC cells, and sinobine hydrochloride can inhibit this signaling pathway, thus inhibiting HCC cells. These results provide new potential therapeutic targets for blocking the progression of HCC induced by CXCL12-CXCR4 axis and CCL21-CCR7.
format Online
Article
Text
id pubmed-9289293
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92892932022-07-19 Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride Shen, Conghuan Li, Jianhua Li, Ruidong Ma, Zhenyu Tao, Yifeng Zhang, Quanbao Wang, Zhengxin Front Oncol Oncology Currently, chemokines and their receptors, CXCL12-CXCR4 and CCL21-CCR7 axes, are deemed vital factors in the modulation of angiogenesis and are crucial for the growth and development of liver cancer. Tumor-derived DNA can be recognized by immune cells to induce an autoimmune response. In this study, we demonstrated the mechanism of tumor-derived DNA on the CXCL12-CXCR4 and CCL21-CCR7 axes of hepatocellular carcinoma (HCC) cells and the regulatory effect of sinomenine hydrochloride. Tumor-derived DNA was separated from HCCLM cell lines. Tumor-derived DNA was transfected into SK-Hep1 cells by Lipofectamine 2000. We found that sinomenine hydrochloride reduced the expression of CXCR4, CXCR12, CCR7, and CCL21 in HCC cells, suppressed the growth and invasion of HCC cells, and increased apoptosis. In contrast to the controls, the protein expressions of CXCR4, CXCL12, CCR7, CCL21, P-ERK1/2, MMP-9, and MMP-2 in SK-Hep1 cells were significantly increased after transfection of tumor-derived DNA, while the increase was reversed by sinobine hydrochloride. Acid sinomenine interferes with tumor-derived DNA and affects ERK/MMP signaling via the CXCL12/CXCR4 axis in HCC cells. CXCR4 siRNA and CCR7 siRNA attenuated tumor-derived DNA activation of ERK1/2/MMP2/9 signaling pathways in HCC cells. CXCR4-oe and CCR7-OE enhance the stimulation of erK1/2/MMP2/9 signaling pathway by tumor-derived DNA in HCC cells. Tumor-derived DNA reduced apoptosis and increased invasion of SK-Hep1 cells by CXCL12-CXCR4 axis and CCL21-CCR7 axis, and sinobine hydrochloride reversed this regulation. These results strongly suggest that tumor-derived DNA can increase the growth and invasion of oncocytes via the upregulation of the expression of CXCL12-CXCR4 and CCL21-CCR7 axis and through ERK1/2/MMP2/9 signaling pathway in HCC cells, and sinobine hydrochloride can inhibit this signaling pathway, thus inhibiting HCC cells. These results provide new potential therapeutic targets for blocking the progression of HCC induced by CXCL12-CXCR4 axis and CCL21-CCR7. Frontiers Media S.A. 2022-07-04 /pmc/articles/PMC9289293/ /pubmed/35860597 http://dx.doi.org/10.3389/fonc.2022.901705 Text en Copyright © 2022 Shen, Li, Li, Ma, Tao, Zhang and Wang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Shen, Conghuan
Li, Jianhua
Li, Ruidong
Ma, Zhenyu
Tao, Yifeng
Zhang, Quanbao
Wang, Zhengxin
Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title_full Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title_fullStr Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title_full_unstemmed Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title_short Effects of Tumor-Derived DNA on CXCL12-CXCR4 and CCL21-CCR7 Axes of Hepatocellular Carcinoma Cells and the Regulation of Sinomenine Hydrochloride
title_sort effects of tumor-derived dna on cxcl12-cxcr4 and ccl21-ccr7 axes of hepatocellular carcinoma cells and the regulation of sinomenine hydrochloride
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289293/
https://www.ncbi.nlm.nih.gov/pubmed/35860597
http://dx.doi.org/10.3389/fonc.2022.901705
work_keys_str_mv AT shenconghuan effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT lijianhua effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT liruidong effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT mazhenyu effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT taoyifeng effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT zhangquanbao effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride
AT wangzhengxin effectsoftumorderiveddnaoncxcl12cxcr4andccl21ccr7axesofhepatocellularcarcinomacellsandtheregulationofsinomeninehydrochloride