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Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma

Cathelicidin hCAP18/LL-37 can resist infection from various pathogens and is an essential component of the human immune system. Accumulating evidence has indicated that hCAP18/LL-37 plays a tissue-specific role in human cancer. However, its function in hepatocellular carcinoma (HCC) is poorly unders...

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Autores principales: Zhang, Huidan, Zhen, Junai, Zhang, Rong, Wanyan, Yangke, Liu, Kehang, Yuan, Xueli, Tao, Liping, Chen, Yuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763942/
https://www.ncbi.nlm.nih.gov/pubmed/35039485
http://dx.doi.org/10.1038/s41420-022-00816-w
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author Zhang, Huidan
Zhen, Junai
Zhang, Rong
Wanyan, Yangke
Liu, Kehang
Yuan, Xueli
Tao, Liping
Chen, Yuqing
author_facet Zhang, Huidan
Zhen, Junai
Zhang, Rong
Wanyan, Yangke
Liu, Kehang
Yuan, Xueli
Tao, Liping
Chen, Yuqing
author_sort Zhang, Huidan
collection PubMed
description Cathelicidin hCAP18/LL-37 can resist infection from various pathogens and is an essential component of the human immune system. Accumulating evidence has indicated that hCAP18/LL-37 plays a tissue-specific role in human cancer. However, its function in hepatocellular carcinoma (HCC) is poorly understood. The present study investigated the effects of hCAP18/LL-37 on HCC in vitro and in vivo. Results showed that hCAP18/LL-37 overexpression significantly promoted the proliferation of cultured HCC cells and the growth of PLC/PRF-5 xenograft tumor. Transcriptome sequencing analyses revealed that the PI3K/Akt pathway was the most significant upregulated pathway induced by LL-37 overexpression. Further analysis demonstrated that hCAP18/LL-37 stimulated the phosphorylation of EGFR/HER2 and activated the PI3K/Akt pathway in HCC cells. Furthermore, stronger EGFR/HER2/Akt signals were observed in the PLC/PRF-5(LL-37) xenograft tumor. Interestingly, even though the expression of hCAP18/LL-37 was significantly downregulated in HCC cells and tumors, 1,25(OH)(2)D(3) treatment significantly upregulated the hCAP18/LL-37 level both in HCC cells and xenograft tumors. Moreover, 1,25(OH)(2)D(3) together with si-LL-37 significantly enhanced the antitumor activity of 1,25(OH)(2)D(3) in the PLC/PRF-5 xenograft tumor. Collectively, these data suggest that hCAP18/LL-37 promotes HCC cells proliferation through stimulation of the EGFR/HER2/Akt signals and appears to suppress the antitumor activity of 1,25(OH)(2)D(3) in HCC xenograft tumor. This implies that hCAP18/LL-37 may be an important target when aiming to improve the antitumor activity of 1,25(OH)(2)D(3) supplementation therapy in HCC.
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spelling pubmed-87639422022-02-04 Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma Zhang, Huidan Zhen, Junai Zhang, Rong Wanyan, Yangke Liu, Kehang Yuan, Xueli Tao, Liping Chen, Yuqing Cell Death Discov Article Cathelicidin hCAP18/LL-37 can resist infection from various pathogens and is an essential component of the human immune system. Accumulating evidence has indicated that hCAP18/LL-37 plays a tissue-specific role in human cancer. However, its function in hepatocellular carcinoma (HCC) is poorly understood. The present study investigated the effects of hCAP18/LL-37 on HCC in vitro and in vivo. Results showed that hCAP18/LL-37 overexpression significantly promoted the proliferation of cultured HCC cells and the growth of PLC/PRF-5 xenograft tumor. Transcriptome sequencing analyses revealed that the PI3K/Akt pathway was the most significant upregulated pathway induced by LL-37 overexpression. Further analysis demonstrated that hCAP18/LL-37 stimulated the phosphorylation of EGFR/HER2 and activated the PI3K/Akt pathway in HCC cells. Furthermore, stronger EGFR/HER2/Akt signals were observed in the PLC/PRF-5(LL-37) xenograft tumor. Interestingly, even though the expression of hCAP18/LL-37 was significantly downregulated in HCC cells and tumors, 1,25(OH)(2)D(3) treatment significantly upregulated the hCAP18/LL-37 level both in HCC cells and xenograft tumors. Moreover, 1,25(OH)(2)D(3) together with si-LL-37 significantly enhanced the antitumor activity of 1,25(OH)(2)D(3) in the PLC/PRF-5 xenograft tumor. Collectively, these data suggest that hCAP18/LL-37 promotes HCC cells proliferation through stimulation of the EGFR/HER2/Akt signals and appears to suppress the antitumor activity of 1,25(OH)(2)D(3) in HCC xenograft tumor. This implies that hCAP18/LL-37 may be an important target when aiming to improve the antitumor activity of 1,25(OH)(2)D(3) supplementation therapy in HCC. Nature Publishing Group UK 2022-01-17 /pmc/articles/PMC8763942/ /pubmed/35039485 http://dx.doi.org/10.1038/s41420-022-00816-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhang, Huidan
Zhen, Junai
Zhang, Rong
Wanyan, Yangke
Liu, Kehang
Yuan, Xueli
Tao, Liping
Chen, Yuqing
Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title_full Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title_fullStr Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title_full_unstemmed Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title_short Cathelicidin hCAP18/LL-37 promotes cell proliferation and suppresses antitumor activity of 1,25(OH)(2)D(3) in hepatocellular carcinoma
title_sort cathelicidin hcap18/ll-37 promotes cell proliferation and suppresses antitumor activity of 1,25(oh)(2)d(3) in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763942/
https://www.ncbi.nlm.nih.gov/pubmed/35039485
http://dx.doi.org/10.1038/s41420-022-00816-w
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