Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma

Abstract Objective To study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. Methods ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver ti...

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Autores principales: Zhou-wei Xu, Na-na Liu, Xing-yu Wang, Bai-cheng Ding, Hai-feng Zhang, Ying Li, Wu-yi Sun, Wei Wei
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Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/9347a35154ff4a76b91f4a5ae2ffd191
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spelling oai:doaj.org-article:9347a35154ff4a76b91f4a5ae2ffd1912021-11-08T11:13:38ZEffect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma10.1186/s12935-021-02261-81475-2867https://doaj.org/article/9347a35154ff4a76b91f4a5ae2ffd1912021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02261-8https://doaj.org/toc/1475-2867Abstract Objective To study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. Methods ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-β1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-β1 and CaM in the cells. Then PLC-β1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue. Results The expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-β1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-β1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue. Conclusion AT1R, PLC-β1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-β1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.Zhou-wei XuNa-na LiuXing-yu WangBai-cheng DingHai-feng ZhangYing LiWu-yi SunWei WeiBMCarticleHepatocellular carcinomaAT1RPLC-β1CaMMigrationInvasionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-21 (2021)
institution DOAJ
collection DOAJ
language EN
topic Hepatocellular carcinoma
AT1R
PLC-β1
CaM
Migration
Invasion
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle Hepatocellular carcinoma
AT1R
PLC-β1
CaM
Migration
Invasion
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Zhou-wei Xu
Na-na Liu
Xing-yu Wang
Bai-cheng Ding
Hai-feng Zhang
Ying Li
Wu-yi Sun
Wei Wei
Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
description Abstract Objective To study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. Methods ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-β1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-β1 and CaM in the cells. Then PLC-β1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue. Results The expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-β1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-β1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue. Conclusion AT1R, PLC-β1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-β1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.
format article
author Zhou-wei Xu
Na-na Liu
Xing-yu Wang
Bai-cheng Ding
Hai-feng Zhang
Ying Li
Wu-yi Sun
Wei Wei
author_facet Zhou-wei Xu
Na-na Liu
Xing-yu Wang
Bai-cheng Ding
Hai-feng Zhang
Ying Li
Wu-yi Sun
Wei Wei
author_sort Zhou-wei Xu
title Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
title_short Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
title_full Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
title_fullStr Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
title_full_unstemmed Effect of PLC- β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma
title_sort effect of plc- β1/cam signaling pathway mediated by at1r on the occurrence and development of hepatocellular carcinoma
publisher BMC
publishDate 2021
url https://doaj.org/article/9347a35154ff4a76b91f4a5ae2ffd191
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