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A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation
Drug repositioning offers new clinical applications for existing drugs with shorter approval processes and lower costs and risks than de novo experimental drug development. The Fufang-Biejia-Ruangan pill (FBRP) is the first clinically approved anti-fibrosis herbal formula in China. Whether FBRP coul...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society of Gene & Cell Therapy
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994416/ https://www.ncbi.nlm.nih.gov/pubmed/31982775 http://dx.doi.org/10.1016/j.omtn.2019.12.023 |
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author | Zhang, Yanqiong Mao, Xia Chen, Wenjia Guo, Xiaodong Yu, Liangxiang Jiang, Funeng Wang, Xiaoyue Li, Weijie Guo, Qiuyan Li, Taixian Lin, Na |
author_facet | Zhang, Yanqiong Mao, Xia Chen, Wenjia Guo, Xiaodong Yu, Liangxiang Jiang, Funeng Wang, Xiaoyue Li, Weijie Guo, Qiuyan Li, Taixian Lin, Na |
author_sort | Zhang, Yanqiong |
collection | PubMed |
description | Drug repositioning offers new clinical applications for existing drugs with shorter approval processes and lower costs and risks than de novo experimental drug development. The Fufang-Biejia-Ruangan pill (FBRP) is the first clinically approved anti-fibrosis herbal formula in China. Whether FBRP could be used to treat hepatocellular carcinoma (HCC) remains unclear. Herein, a total of 161 FBRP candidate targets against HCC were identified according to the topological importance in the “hepatic fibrosis-cirrhosis-cancer axis-related gene-FBRP putative target” network, and mostly enriched in phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor κB (NF-κB) signaling. Experimentally, FBRP inhibited liver fibrosis and prevented the development of neoplastic lesions at the early stages of hepatocarcinogenesis in a diethylnitrosamine-induced rat HCC model. FBRP inhibited tumor cell proliferation, induced tumor-specific cell death, and suppressed tumor progression in HCC rats while preventing the activation of PI3K, AKT and IKΚB proteins, reducing the nuclear accumulation of NFΚB1 protein, and decreasing the downstream expression of proteins. Consistently, FBRP suppressed HCC cell proliferation and induced cell cycle arrest in vitro. Co-treatment of FBRP with PI3K inhibitor exhibited an additive inhibitory effect on PI3K/AKT/NF-κB activation. Collectively, our data showed the potentials of FBRP in hepatic fibrosis microenvironment regulation and tumor prevention, suggesting that FBRP may be a promising candidate drug for reduction of fibrogenesis and prevention of HCC. |
format | Online Article Text |
id | pubmed-6994416 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-69944162020-02-04 A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation Zhang, Yanqiong Mao, Xia Chen, Wenjia Guo, Xiaodong Yu, Liangxiang Jiang, Funeng Wang, Xiaoyue Li, Weijie Guo, Qiuyan Li, Taixian Lin, Na Mol Ther Nucleic Acids Article Drug repositioning offers new clinical applications for existing drugs with shorter approval processes and lower costs and risks than de novo experimental drug development. The Fufang-Biejia-Ruangan pill (FBRP) is the first clinically approved anti-fibrosis herbal formula in China. Whether FBRP could be used to treat hepatocellular carcinoma (HCC) remains unclear. Herein, a total of 161 FBRP candidate targets against HCC were identified according to the topological importance in the “hepatic fibrosis-cirrhosis-cancer axis-related gene-FBRP putative target” network, and mostly enriched in phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear factor κB (NF-κB) signaling. Experimentally, FBRP inhibited liver fibrosis and prevented the development of neoplastic lesions at the early stages of hepatocarcinogenesis in a diethylnitrosamine-induced rat HCC model. FBRP inhibited tumor cell proliferation, induced tumor-specific cell death, and suppressed tumor progression in HCC rats while preventing the activation of PI3K, AKT and IKΚB proteins, reducing the nuclear accumulation of NFΚB1 protein, and decreasing the downstream expression of proteins. Consistently, FBRP suppressed HCC cell proliferation and induced cell cycle arrest in vitro. Co-treatment of FBRP with PI3K inhibitor exhibited an additive inhibitory effect on PI3K/AKT/NF-κB activation. Collectively, our data showed the potentials of FBRP in hepatic fibrosis microenvironment regulation and tumor prevention, suggesting that FBRP may be a promising candidate drug for reduction of fibrogenesis and prevention of HCC. American Society of Gene & Cell Therapy 2020-01-10 /pmc/articles/PMC6994416/ /pubmed/31982775 http://dx.doi.org/10.1016/j.omtn.2019.12.023 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Zhang, Yanqiong Mao, Xia Chen, Wenjia Guo, Xiaodong Yu, Liangxiang Jiang, Funeng Wang, Xiaoyue Li, Weijie Guo, Qiuyan Li, Taixian Lin, Na A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title | A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title_full | A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title_fullStr | A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title_full_unstemmed | A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title_short | A Discovery of Clinically Approved Formula FBRP for Repositioning to Treat HCC by Inhibiting PI3K/AKT/NF-κB Activation |
title_sort | discovery of clinically approved formula fbrp for repositioning to treat hcc by inhibiting pi3k/akt/nf-κb activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994416/ https://www.ncbi.nlm.nih.gov/pubmed/31982775 http://dx.doi.org/10.1016/j.omtn.2019.12.023 |
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