Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer

Objective The objective of this study was to investigate the inhibitory effect of sophocarpine on the progression of castration-resistant prostate cancer (CRPC) and the underlying molecular mechanism. Methods DU145 and PC3 cells (two CRPC cell lines), incubated with different concentrations of sopho...

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Main Authors: Min Weng, Chenghao Shi, Hui Han, Hengyue Zhu, Yanyi Xiao, Hangcheng Guo, Zhixian Yu, Cunzao Wu
Format: Article
Language:English
Published: PeerJ Inc. 2022-09-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/14042.pdf
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author Min Weng
Chenghao Shi
Hui Han
Hengyue Zhu
Yanyi Xiao
Hangcheng Guo
Zhixian Yu
Cunzao Wu
author_facet Min Weng
Chenghao Shi
Hui Han
Hengyue Zhu
Yanyi Xiao
Hangcheng Guo
Zhixian Yu
Cunzao Wu
author_sort Min Weng
collection DOAJ
description Objective The objective of this study was to investigate the inhibitory effect of sophocarpine on the progression of castration-resistant prostate cancer (CRPC) and the underlying molecular mechanism. Methods DU145 and PC3 cells (two CRPC cell lines), incubated with different concentrations of sophocarpine, were used. Cell Counting Kit-8 assay, real-time cellular analysis, and colony formation assay were conducted to evaluate the proliferation of CRPC cells. Cytometry flow analysis was performed to evaluate the apoptosis rate of CRPC cells. Wound healing and Transwell invasion assays were performed and the levels of the epithelial-mesenchymal transition (EMT)-related proteins were determined to analyze cell migration and invasion abilities. A xenografted tumor model of nude mice was used to examine the anti-cancer effect of sophocarpine on CRPC. Western blotting was performed to evaluate the activities of the PI3K/AKT/mTOR signaling pathway both in cells and tumor tissues. Results In vitro tests showed that sophocarpine suppressed the proliferation of CRPC cells, reduced the migration and invasion abilities, and increased the apoptosis rate. In vivo, sophocarpine decreased the weight and volume of tumor tissues. Mechanically, sophocarpine exerted its anti-cancer effects by inactivating PI3K/AKT/mTOR signaling. Conclusion Sophocarpine inhibited the progression of CRPC by downregulating the PI3K/AKT/mTOR signaling pathway and showed a potential to be an anti-cancer agent against CRPC.
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spelling doaj.art-995d841ddb674817be35f446e6ed422b2023-12-02T21:50:33ZengPeerJ Inc.PeerJ2167-83592022-09-0110e1404210.7717/peerj.14042Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancerMin Weng0Chenghao Shi1Hui Han2Hengyue Zhu3Yanyi Xiao4Hangcheng Guo5Zhixian Yu6Cunzao Wu7Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaObjective The objective of this study was to investigate the inhibitory effect of sophocarpine on the progression of castration-resistant prostate cancer (CRPC) and the underlying molecular mechanism. Methods DU145 and PC3 cells (two CRPC cell lines), incubated with different concentrations of sophocarpine, were used. Cell Counting Kit-8 assay, real-time cellular analysis, and colony formation assay were conducted to evaluate the proliferation of CRPC cells. Cytometry flow analysis was performed to evaluate the apoptosis rate of CRPC cells. Wound healing and Transwell invasion assays were performed and the levels of the epithelial-mesenchymal transition (EMT)-related proteins were determined to analyze cell migration and invasion abilities. A xenografted tumor model of nude mice was used to examine the anti-cancer effect of sophocarpine on CRPC. Western blotting was performed to evaluate the activities of the PI3K/AKT/mTOR signaling pathway both in cells and tumor tissues. Results In vitro tests showed that sophocarpine suppressed the proliferation of CRPC cells, reduced the migration and invasion abilities, and increased the apoptosis rate. In vivo, sophocarpine decreased the weight and volume of tumor tissues. Mechanically, sophocarpine exerted its anti-cancer effects by inactivating PI3K/AKT/mTOR signaling. Conclusion Sophocarpine inhibited the progression of CRPC by downregulating the PI3K/AKT/mTOR signaling pathway and showed a potential to be an anti-cancer agent against CRPC.https://peerj.com/articles/14042.pdfCastration-resistant prostate cancerSophocarpinemTORProliferationEpithelial-mesenchymal transition
spellingShingle Min Weng
Chenghao Shi
Hui Han
Hengyue Zhu
Yanyi Xiao
Hangcheng Guo
Zhixian Yu
Cunzao Wu
Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
PeerJ
Castration-resistant prostate cancer
Sophocarpine
mTOR
Proliferation
Epithelial-mesenchymal transition
title Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
title_full Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
title_fullStr Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
title_full_unstemmed Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
title_short Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer
title_sort sophocarpine inhibits tumor progression by antagonizing the pi3k akt mtor signaling pathway in castration resistant prostate cancer
topic Castration-resistant prostate cancer
Sophocarpine
mTOR
Proliferation
Epithelial-mesenchymal transition
url https://peerj.com/articles/14042.pdf
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