Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway

Abstract In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific...

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Autores principales: Huayuan Liu, Caiyun Liu, Mengya Wang, Dongxu Sun, Pengcheng Zhu, Ping Zhang, Xueying Tan, Guangjun Shi
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/314a9d98aeea42ee9c016ffa34b510b7
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spelling oai:doaj.org-article:314a9d98aeea42ee9c016ffa34b510b72021-12-02T18:51:36ZTanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway10.1038/s41598-021-98948-z2045-2322https://doaj.org/article/314a9d98aeea42ee9c016ffa34b510b72021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98948-zhttps://doaj.org/toc/2045-2322Abstract In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein–protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.Huayuan LiuCaiyun LiuMengya WangDongxu SunPengcheng ZhuPing ZhangXueying TanGuangjun ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Huayuan Liu
Caiyun Liu
Mengya Wang
Dongxu Sun
Pengcheng Zhu
Ping Zhang
Xueying Tan
Guangjun Shi
Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
description Abstract In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein–protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.
format article
author Huayuan Liu
Caiyun Liu
Mengya Wang
Dongxu Sun
Pengcheng Zhu
Ping Zhang
Xueying Tan
Guangjun Shi
author_facet Huayuan Liu
Caiyun Liu
Mengya Wang
Dongxu Sun
Pengcheng Zhu
Ping Zhang
Xueying Tan
Guangjun Shi
author_sort Huayuan Liu
title Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
title_short Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
title_full Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
title_fullStr Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
title_full_unstemmed Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway
title_sort tanshinone iia affects the malignant growth of cholangiocarcinoma cells by inhibiting the pi3k-akt-mtor pathway
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/314a9d98aeea42ee9c016ffa34b510b7
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