Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells

Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the...

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Autores principales:	Yaru Li, Yilong Zhu, Jicheng Han, Jinbo Fang, Zhiru Xiu, Shanzhi Li, Wenjie Li, Xia Yang, Ningyi Jin, Lili Sun, Xiao Li, Yiquan Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	adriamycin resistance oncolytic adenovirus breast cancer toxicity autophagy Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/922dea3a9c7d4cb5aae5c856279421d5
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spelling	oai:doaj.org-article:922dea3a9c7d4cb5aae5c856279421d52021-11-19T06:12:21ZAd-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells2296-889X10.3389/fmolb.2021.763500https://doaj.org/article/922dea3a9c7d4cb5aae5c856279421d52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.763500/fullhttps://doaj.org/toc/2296-889XAd-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of breast cancer cells to chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of Adriamycin-resistant breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of breast cancer cells to Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to adriamycin, which is caused by the reduction of MRP1 protein level in MCF-7/ADR cells after treatment with Ad-VT, and MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to Adriamycin. Therefore, the combination of Ad-VT and chemotherapy drugs may become a new strategy for the treatment of breast cancer in overcoming Adriamycin resistance.Yaru LiYaru LiYaru LiYilong ZhuJicheng HanJinbo FangZhiru XiuShanzhi LiWenjie LiXia YangXia YangXia YangNingyi JinNingyi JinNingyi JinLili SunLili SunXiao LiXiao LiXiao LiYiquan LiYiquan LiYiquan LiFrontiers Media S.A.articleadriamycin resistanceoncolytic adenovirusbreast cancertoxicityautophagyBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adriamycin resistance oncolytic adenovirus breast cancer toxicity autophagy Biology (General) QH301-705.5
spellingShingle	adriamycin resistance oncolytic adenovirus breast cancer toxicity autophagy Biology (General) QH301-705.5 Yaru Li Yaru Li Yaru Li Yilong Zhu Jicheng Han Jinbo Fang Zhiru Xiu Shanzhi Li Wenjie Li Xia Yang Xia Yang Xia Yang Ningyi Jin Ningyi Jin Ningyi Jin Lili Sun Lili Sun Xiao Li Xiao Li Xiao Li Yiquan Li Yiquan Li Yiquan Li Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
description	Ad-VT (Ad-Apoptin-hTERTp-E1a) is a type of oncolytic adenovirus with dual specific tumor cell death ability. It can effectively induce cell death of breast cancer cells and has better effect when used in combination with chemotherapy drugs. However, it has not been reported whether Ad-VT reduces the resistance of breast cancer cells to chemotherapy drugs. The purpose of this study is to investigate the effect of Ad-VT on drug resistance of Adriamycin-resistant breast cancer cells. For this, the effects of different doses of Ad-VT on the resistance of breast cancer cells to Adriamycin were analyzed using qualitative and quantitative experiments in vitro and in vivo. The Ad-VT can reduce the resistance of MCF-7/ADR to adriamycin, which is caused by the reduction of MRP1 protein level in MCF-7/ADR cells after treatment with Ad-VT, and MRP1 can be interfered with by autophagy inhibitors. Subsequently, the upstream signal of autophagy was analyzed and it was found that Ad-VT reduced the resistance of cells to doxorubicin by reducing the level of mTOR, and then the analysis of the upstream and downstream proteins of mTOR found that Ad-VT increased the sensitivity of MCF-7/ADR cells to adriamycin by activating AMPK-mTOR-eIF4F signaling axis. Ad-VT can not only significantly induce cell death in MCF-7/ADR cells, but also improved their sensitivity to Adriamycin. Therefore, the combination of Ad-VT and chemotherapy drugs may become a new strategy for the treatment of breast cancer in overcoming Adriamycin resistance.
format	article
author	Yaru Li Yaru Li Yaru Li Yilong Zhu Jicheng Han Jinbo Fang Zhiru Xiu Shanzhi Li Wenjie Li Xia Yang Xia Yang Xia Yang Ningyi Jin Ningyi Jin Ningyi Jin Lili Sun Lili Sun Xiao Li Xiao Li Xiao Li Yiquan Li Yiquan Li Yiquan Li
author_facet	Yaru Li Yaru Li Yaru Li Yilong Zhu Jicheng Han Jinbo Fang Zhiru Xiu Shanzhi Li Wenjie Li Xia Yang Xia Yang Xia Yang Ningyi Jin Ningyi Jin Ningyi Jin Lili Sun Lili Sun Xiao Li Xiao Li Xiao Li Yiquan Li Yiquan Li Yiquan Li
author_sort	Yaru Li
title	Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
title_short	Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
title_full	Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
title_fullStr	Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
title_full_unstemmed	Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells
title_sort	ad-apoptin-htertp-e1a regulates autophagy through the ampk-mtor-eif4f signaling axis to reduce drug resistance of mcf-7/adr cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/922dea3a9c7d4cb5aae5c856279421d5
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Ad-Apoptin-hTERTp-E1a Regulates Autophagy Through the AMPK-mTOR-eIF4F Signaling Axis to Reduce Drug Resistance of MCF-7/ADR Cells

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