A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer

Mengmeng Dong,1,2,* Jiawen Chen,2,* Jiayuan Zhang,2 Xiao Liang,2 Jiebing Yang,2 Dan Li,1 Quanshun Li2 1Department of Cancer Center, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of...

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Autores principales: Dong M, Chen J, Zhang J, Liang X, Yang J, Li D, Li Q
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:a094f105426b46cfb2d8ec5a7ab8c9272021-12-02T02:23:22ZA chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer1178-2013https://doaj.org/article/a094f105426b46cfb2d8ec5a7ab8c9272019-02-01T00:00:00Zhttps://www.dovepress.com/a-chemoenzymatically-synthesized-cholesterol-g-polyamine-co-ester-medi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mengmeng Dong,1,2,* Jiawen Chen,2,* Jiayuan Zhang,2 Xiao Liang,2 Jiebing Yang,2 Dan Li,1 Quanshun Li2 1Department of Cancer Center, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of China *These authors contributed equally to this work Background: An amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model. Materials and methods: The transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays. Results: The transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection. Conclusion: Chol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response. Keywords: cholesterol-g-poly(amine-co-ester), p53 gene delivery, gene therapy, anti-proliferation effect, anti-migration effectDong MChen JZhang JLiang XYang JLi DLi QDove Medical Pressarticlecholesterol-g-poly(amine-co-ester)p53 gene deliverygene therapyanti-proliferation effectanti-migration effectMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1149-1161 (2019)
institution DOAJ
collection DOAJ
language EN
topic cholesterol-g-poly(amine-co-ester)
p53 gene delivery
gene therapy
anti-proliferation effect
anti-migration effect
Medicine (General)
R5-920
spellingShingle cholesterol-g-poly(amine-co-ester)
p53 gene delivery
gene therapy
anti-proliferation effect
anti-migration effect
Medicine (General)
R5-920
Dong M
Chen J
Zhang J
Liang X
Yang J
Li D
Li Q
A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
description Mengmeng Dong,1,2,* Jiawen Chen,2,* Jiayuan Zhang,2 Xiao Liang,2 Jiebing Yang,2 Dan Li,1 Quanshun Li2 1Department of Cancer Center, The First Hospital of Jilin University, Changchun 130021, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of China *These authors contributed equally to this work Background: An amphiphilic cationic copolymer cholesterol-g-poly(amine-co-ester), namely Chol-g-PMSC-PPDL synthesized in a chemoenzymatic route has been utilized as a carrier for p53 gene delivery to check its antitumor efficacy, using human prostate cancer cell line PC-3 (p53 null) as a model. Materials and methods: The transfection efficiency was measured by quantitative PCR and Western blotting assay. The anti-proliferative effect was detected using MTT method, colony formation assay and Live/Dead staining. The anti-migration effect was evaluated through wound healing and Transwell migration assays. Results: The transfection efficiency assay indicated that the carrier-mediated p53 gene transfection could dramatically enhance the intracellular p53 expression level. Through p53 gene delivery, obvious anti-proliferative effect could be detected which was elucidated to be associated with the simultaneous activation of mitochondrial-dependent apoptosis pathway and cell cycle arrest at G1 phase. Meanwhile, the anti-migration effect could be obtained after p53 gene transfection. Conclusion: Chol-g-PMSC-PPDL-mediated p53 gene transfection could potentially be employed as a promising strategy for achieving effective anti-tumor response. Keywords: cholesterol-g-poly(amine-co-ester), p53 gene delivery, gene therapy, anti-proliferation effect, anti-migration effect
format article
author Dong M
Chen J
Zhang J
Liang X
Yang J
Li D
Li Q
author_facet Dong M
Chen J
Zhang J
Liang X
Yang J
Li D
Li Q
author_sort Dong M
title A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
title_short A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
title_full A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
title_fullStr A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
title_full_unstemmed A chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
title_sort chemoenzymatically synthesized cholesterol-g-poly(amine-co-ester)-mediated p53 gene delivery for achieving antitumor efficacy in prostate cancer
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/a094f105426b46cfb2d8ec5a7ab8c927
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