Cargando…

Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model

Oncolytic adenovirus (OA) has attracted increasing attention due to their specific proliferation in tumour cells and resulting in lysis of tumour cells. To further improve the antitumour effect of OA, in this study, we combined CD55‐TRAIL‐IETD‐MnSOD (CD55‐TMn), a CEA‐controlled OA constructed previo...

Descripción completa

Detalles Bibliográficos
Autores principales: Xiao, Boduan, Ying, Chang, Chen, Yongyi, Huang, Fang, Wang, Binrong, Fang, Huiling, Guo, Wan, Liu, Tao, Zhou, Xiumei, Huang, Biao, Liu, Xinyuan, Wang, Yigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701578/
https://www.ncbi.nlm.nih.gov/pubmed/33251723
http://dx.doi.org/10.1111/jcmm.15966
_version_ 1783616495646932992
author Xiao, Boduan
Ying, Chang
Chen, Yongyi
Huang, Fang
Wang, Binrong
Fang, Huiling
Guo, Wan
Liu, Tao
Zhou, Xiumei
Huang, Biao
Liu, Xinyuan
Wang, Yigang
author_facet Xiao, Boduan
Ying, Chang
Chen, Yongyi
Huang, Fang
Wang, Binrong
Fang, Huiling
Guo, Wan
Liu, Tao
Zhou, Xiumei
Huang, Biao
Liu, Xinyuan
Wang, Yigang
author_sort Xiao, Boduan
collection PubMed
description Oncolytic adenovirus (OA) has attracted increasing attention due to their specific proliferation in tumour cells and resulting in lysis of tumour cells. To further improve the antitumour effect of OA, in this study, we combined CD55‐TRAIL‐IETD‐MnSOD (CD55‐TMn), a CEA‐controlled OA constructed previously, and chemotherapy to investigate their synergistic effect and possible mechanisms. MTT assay was performed to detect antitumour effects. Hoechst 33 342 and flow cytometric analysis were used to examine cell apoptosis. Western blotting was performed to examine cell pyroptosis and apoptosis mechanism. Animal experiment was used to detect antitumour effect of doxorubicin hydrochloride (Dox) combined with CD55‐TMn in vivo. We firstly found that Dox promotes gene expression mediated by CEA‐regulated OA and virus progeny replication by activating phosphorylation of Smad3, and Dox can enhance antitumour effect of CEA‐regulated CD55‐TMn by promoting cell apotopsis and cell pyroptosis. Thus, our results provide an experimental and theoretical basis on tumour therapy by combination treatment of the oncolytic virotherapy and chemotherapy and it is expected to become a novel strategy for liver cancer therapy.
format Online
Article
Text
id pubmed-7701578
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-77015782020-12-08 Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model Xiao, Boduan Ying, Chang Chen, Yongyi Huang, Fang Wang, Binrong Fang, Huiling Guo, Wan Liu, Tao Zhou, Xiumei Huang, Biao Liu, Xinyuan Wang, Yigang J Cell Mol Med Original Articles Oncolytic adenovirus (OA) has attracted increasing attention due to their specific proliferation in tumour cells and resulting in lysis of tumour cells. To further improve the antitumour effect of OA, in this study, we combined CD55‐TRAIL‐IETD‐MnSOD (CD55‐TMn), a CEA‐controlled OA constructed previously, and chemotherapy to investigate their synergistic effect and possible mechanisms. MTT assay was performed to detect antitumour effects. Hoechst 33 342 and flow cytometric analysis were used to examine cell apoptosis. Western blotting was performed to examine cell pyroptosis and apoptosis mechanism. Animal experiment was used to detect antitumour effect of doxorubicin hydrochloride (Dox) combined with CD55‐TMn in vivo. We firstly found that Dox promotes gene expression mediated by CEA‐regulated OA and virus progeny replication by activating phosphorylation of Smad3, and Dox can enhance antitumour effect of CEA‐regulated CD55‐TMn by promoting cell apotopsis and cell pyroptosis. Thus, our results provide an experimental and theoretical basis on tumour therapy by combination treatment of the oncolytic virotherapy and chemotherapy and it is expected to become a novel strategy for liver cancer therapy. John Wiley and Sons Inc. 2020-10-14 2020-11 /pmc/articles/PMC7701578/ /pubmed/33251723 http://dx.doi.org/10.1111/jcmm.15966 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://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
Xiao, Boduan
Ying, Chang
Chen, Yongyi
Huang, Fang
Wang, Binrong
Fang, Huiling
Guo, Wan
Liu, Tao
Zhou, Xiumei
Huang, Biao
Liu, Xinyuan
Wang, Yigang
Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title_full Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title_fullStr Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title_full_unstemmed Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title_short Doxorubicin hydrochloride enhanced antitumour effect of CEA‐regulated oncolytic virotherapy in live cancer cells and a mouse model
title_sort doxorubicin hydrochloride enhanced antitumour effect of cea‐regulated oncolytic virotherapy in live cancer cells and a mouse model
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701578/
https://www.ncbi.nlm.nih.gov/pubmed/33251723
http://dx.doi.org/10.1111/jcmm.15966
work_keys_str_mv AT xiaoboduan doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT yingchang doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT chenyongyi doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT huangfang doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT wangbinrong doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT fanghuiling doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT guowan doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT liutao doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT zhouxiumei doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT huangbiao doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT liuxinyuan doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel
AT wangyigang doxorubicinhydrochlorideenhancedantitumoureffectofcearegulatedoncolyticvirotherapyinlivecancercellsandamousemodel