Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer

Abstract Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor...

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Autores principales:	Junlian Gu, Yang Li, Jun Zeng, Bo Wang, Kun Ji, Yufeng Tang, Qing Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da643561ff5a439db507a15324c4d9e6
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spelling	oai:doaj.org-article:da643561ff5a439db507a15324c4d9e62021-12-02T11:53:03ZKnockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer10.1038/s41598-017-07973-42045-2322https://doaj.org/article/da643561ff5a439db507a15324c4d9e62017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07973-4https://doaj.org/toc/2045-2322Abstract Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process. The results demonstrated that the treatment of tumor-bearing mice with attenuated Salmonella carrying the HIF-1α siRNA plasmid greatly enhanced the antitumor effects of low-dose DDP. Further mechanistic studies demonstrated that knockdown of HIF-1α improved the response of PCa cells to DDP by redirecting aerobic glycolysis toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of ROS. Our findings indicate that DDP-based chemotherapy combined with targeting the HIF-1α-regulated cancer metabolism pathway might be an ideal strategy to treat PCa.Junlian GuYang LiJun ZengBo WangKun JiYufeng TangQing SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junlian Gu Yang Li Jun Zeng Bo Wang Kun Ji Yufeng Tang Qing Sun Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
description	Abstract Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process. The results demonstrated that the treatment of tumor-bearing mice with attenuated Salmonella carrying the HIF-1α siRNA plasmid greatly enhanced the antitumor effects of low-dose DDP. Further mechanistic studies demonstrated that knockdown of HIF-1α improved the response of PCa cells to DDP by redirecting aerobic glycolysis toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of ROS. Our findings indicate that DDP-based chemotherapy combined with targeting the HIF-1α-regulated cancer metabolism pathway might be an ideal strategy to treat PCa.
format	article
author	Junlian Gu Yang Li Jun Zeng Bo Wang Kun Ji Yufeng Tang Qing Sun
author_facet	Junlian Gu Yang Li Jun Zeng Bo Wang Kun Ji Yufeng Tang Qing Sun
author_sort	Junlian Gu
title	Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
title_short	Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
title_full	Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
title_fullStr	Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
title_full_unstemmed	Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
title_sort	knockdown of hif-1α by sirna-expressing plasmid delivered by attenuated salmonella enhances the antitumor effects of cisplatin on prostate cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/da643561ff5a439db507a15324c4d9e6
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Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer

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