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Cancer Cell International
Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Primary research

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

Authors: Renjie Zhang, Zijian Wang, Wenjie You, Fengfang Zhou, Zicheng Guo, Kaiyu Qian, Yu Xiao, Xinghuan Wang

Published in: Cancer Cell International | Issue 1/2020

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Abstract

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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Metadata
Title
Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT
Authors
Renjie Zhang
Zijian Wang
Wenjie You
Fengfang Zhou
Zicheng Guo
Kaiyu Qian
Yu Xiao
Xinghuan Wang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01607-y

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