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SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway

Bladder cancer (BC) is a major disease of the genitourinary tract, and chemotherapy is one of the main treatments commonly used at present. SC66 is a new type of allosteric AKT inhibitor that is reported to play an effective inhibitory role in the progression of many other types of tumours, but ther...

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Autores principales: Chen, Wu, Zhao, Sheng, Yu, Weimin, Rao, Ting, Ruan, Yuan, Zhu, Shaoming, Xia, Yuqi, Song, Hongfei, Cheng, Fan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581318/
https://www.ncbi.nlm.nih.gov/pubmed/34687144
http://dx.doi.org/10.1111/jcmm.17005
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author Chen, Wu
Zhao, Sheng
Yu, Weimin
Rao, Ting
Ruan, Yuan
Zhu, Shaoming
Xia, Yuqi
Song, Hongfei
Cheng, Fan
author_facet Chen, Wu
Zhao, Sheng
Yu, Weimin
Rao, Ting
Ruan, Yuan
Zhu, Shaoming
Xia, Yuqi
Song, Hongfei
Cheng, Fan
author_sort Chen, Wu
collection PubMed
description Bladder cancer (BC) is a major disease of the genitourinary tract, and chemotherapy is one of the main treatments commonly used at present. SC66 is a new type of allosteric AKT inhibitor that is reported to play an effective inhibitory role in the progression of many other types of tumours, but there is no reported research on its role in BC. In this study, we found that SC66 significantly inhibited the proliferation and EMT‐mediated migration and invasion of T24 and 5637 cells. In addition, experiments confirmed that SC66 achieved its antitumour effect by inducing cell apoptosis and affecting the cell cycle. Luciferase assays confirmed that SC66 exerted an antitumour effect through the AKT/β‐catenin signalling pathway, and this inhibitory effect was reversed after the addition of the β‐catenin signalling pathway activator, CHIR‐99021. In addition, animal studies have shown that, compared with the control group, the experimental group with SC66 intraperitoneal injection showed significantly reduced the tumour weight and volume in nude mice with T24 tumours and that SC66 combined with cisplatin achieved better inhibition on tumours. Western blot analysis and immunohistochemistry staining confirmed that SC66 inhibited the EMT process in vivo and induced apoptosis through the AKT/β‐catenin signalling pathway. In conclusion, our study demonstrated that SC66 exerts a significant antitumour effect through the AKT/β‐catenin signalling pathway, thereby providing a new potential treatment for BC.
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spelling pubmed-85813182021-11-17 SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway Chen, Wu Zhao, Sheng Yu, Weimin Rao, Ting Ruan, Yuan Zhu, Shaoming Xia, Yuqi Song, Hongfei Cheng, Fan J Cell Mol Med Original Articles Bladder cancer (BC) is a major disease of the genitourinary tract, and chemotherapy is one of the main treatments commonly used at present. SC66 is a new type of allosteric AKT inhibitor that is reported to play an effective inhibitory role in the progression of many other types of tumours, but there is no reported research on its role in BC. In this study, we found that SC66 significantly inhibited the proliferation and EMT‐mediated migration and invasion of T24 and 5637 cells. In addition, experiments confirmed that SC66 achieved its antitumour effect by inducing cell apoptosis and affecting the cell cycle. Luciferase assays confirmed that SC66 exerted an antitumour effect through the AKT/β‐catenin signalling pathway, and this inhibitory effect was reversed after the addition of the β‐catenin signalling pathway activator, CHIR‐99021. In addition, animal studies have shown that, compared with the control group, the experimental group with SC66 intraperitoneal injection showed significantly reduced the tumour weight and volume in nude mice with T24 tumours and that SC66 combined with cisplatin achieved better inhibition on tumours. Western blot analysis and immunohistochemistry staining confirmed that SC66 inhibited the EMT process in vivo and induced apoptosis through the AKT/β‐catenin signalling pathway. In conclusion, our study demonstrated that SC66 exerts a significant antitumour effect through the AKT/β‐catenin signalling pathway, thereby providing a new potential treatment for BC. John Wiley and Sons Inc. 2021-10-22 2021-11 /pmc/articles/PMC8581318/ /pubmed/34687144 http://dx.doi.org/10.1111/jcmm.17005 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Chen, Wu
Zhao, Sheng
Yu, Weimin
Rao, Ting
Ruan, Yuan
Zhu, Shaoming
Xia, Yuqi
Song, Hongfei
Cheng, Fan
SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title_full SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title_fullStr SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title_full_unstemmed SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title_short SC66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the AKT/β‐catenin pathway
title_sort sc66 inhibits the proliferation and induces apoptosis of human bladder cancer cells by targeting the akt/β‐catenin pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581318/
https://www.ncbi.nlm.nih.gov/pubmed/34687144
http://dx.doi.org/10.1111/jcmm.17005
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