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

Renjie Zhang; Zijian Wang; Wenjie You; Fengfang Zhou; Zicheng Guo; Kaiyu Qian; Yu Xiao; Xinghuan Wang

doi:10.1186/s12935-020-01607-y

journal article Open Access Oct 27, 2020

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

Renjie Zhang Zijian Wang

Wenjie You Fengfang Zhou Zicheng Guo Kaiyu Qian Yu Xiao

Xinghuan Wang

Cancer Cell International Vol. 20 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1186/s12935-020-01607-y

Abstract

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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Details

Published: Oct 27, 2020
Vol/Issue: 20(1)
License: View

Authors

School of Metallurgical and Ecological Engineering University of Science and Technology Beijing 30, Xueyuan Road, Haidian District Beijing 100083 China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering Chinese Academy of Sciences Beijing 100190 China; Key Laboratory of Biopharmaceutical Preparation and Delivery Chinese Academy of Sciences Beijing 100190 China

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China

Funding

Medical Science Advancement Program (Clinical Medicine) of Wuhan University Award: TFLC2018002

Improvement Project for Theranostic Ability on Difficulty Miscellaneous Disease (Tumor) from National Health Commission of China Award: ZLYNXM202006

Cite This Article

Renjie Zhang, Zijian Wang, Wenjie You, et al. (2020). Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT. Cancer Cell International, 20(1). https://doi.org/10.1186/s12935-020-01607-y

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

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