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Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

BACKGROUND: Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. M...

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Autores principales: Zhang, Renjie, Wang, Zijian, You, Wenjie, Zhou, Fengfang, Guo, Zicheng, Qian, Kaiyu, Xiao, Yu, Wang, Xinghuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590591/
https://www.ncbi.nlm.nih.gov/pubmed/33117085
http://dx.doi.org/10.1186/s12935-020-01607-y
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author Zhang, Renjie
Wang, Zijian
You, Wenjie
Zhou, Fengfang
Guo, Zicheng
Qian, Kaiyu
Xiao, Yu
Wang, Xinghuan
author_facet Zhang, Renjie
Wang, Zijian
You, Wenjie
Zhou, Fengfang
Guo, Zicheng
Qian, Kaiyu
Xiao, Yu
Wang, Xinghuan
author_sort Zhang, Renjie
collection PubMed
description BACKGROUND: Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. METHODS: The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. RESULTS: The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). CONCLUSIONS: In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.
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spelling pubmed-75905912020-10-27 Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT Zhang, Renjie Wang, Zijian You, Wenjie Zhou, Fengfang Guo, Zicheng Qian, Kaiyu Xiao, Yu Wang, Xinghuan Cancer Cell Int Primary Research BACKGROUND: Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. METHODS: The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. RESULTS: The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). CONCLUSIONS: In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy. BioMed Central 2020-10-27 /pmc/articles/PMC7590591/ /pubmed/33117085 http://dx.doi.org/10.1186/s12935-020-01607-y Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Zhang, Renjie
Wang, Zijian
You, Wenjie
Zhou, Fengfang
Guo, Zicheng
Qian, Kaiyu
Xiao, Yu
Wang, Xinghuan
Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title_full Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title_fullStr Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title_full_unstemmed Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title_short Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
title_sort suppressive effects of plumbagin on the growth of human bladder cancer cells via pi3k/akt/mtor signaling pathways and emt
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590591/
https://www.ncbi.nlm.nih.gov/pubmed/33117085
http://dx.doi.org/10.1186/s12935-020-01607-y
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