Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes

Yuzhen Xu,1 Liyan Qiu2 1College of Pharmaceutical Sciences, 2Ministry of Education Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China Abstract: The use of vincristine (VCR) to treat c...

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Autores principales:	Xu YZ, Qiu LY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ff77070bf7824804b1f21aa91db0d51b
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spelling	oai:doaj.org-article:ff77070bf7824804b1f21aa91db0d51b2021-12-02T11:01:34ZNonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes1178-2013https://doaj.org/article/ff77070bf7824804b1f21aa91db0d51b2015-06-01T00:00:00Zhttp://www.dovepress.com/nonspecifically-enhanced-therapeutic-effects-of-vincristine-on-multidr-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yuzhen Xu,1 Liyan Qiu2 1College of Pharmaceutical Sciences, 2Ministry of Education Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China Abstract: The use of vincristine (VCR) to treat cancer has been limited by its dose-dependent toxicity and development of drug resistance after repeated administrations. In this study, we investigated the mechanism by which quinine hydrochloride (QN) acts as a sensitizer for VCR. Our experiments used three kinds of multidrug-resistant cancer cells and demonstrated that QN worked by inducing intracellular depletion of adenosine triphosphate, increasing adenosine triphosphatase activity, and decreasing P-glycoprotein expression. Based on these results, we designed and prepared a VCR and QN codelivery liposome (VQL) and investigated the effect of coencapsulated QN on the in vitro cytotoxicity of VCR in cells and three-dimensional multicellular tumor spheroids. The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice. The results of this in vivo study indicated that VQL could reverse VCR resistance. In addition, it reduced tumor volume 5.4-fold when compared with other test groups. The data suggest that VQL could be a promising nanoscaled therapeutic agent to overcome multidrug resistance, and may have important clinical implications for the treatment of cancer. Keywords: vincristine, quinine, combination therapy, liposome, multidrug resistance reversal, P-glycoprotein Xu YZQiu LYDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4225-4237 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Xu YZ Qiu LY Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
description	Yuzhen Xu,1 Liyan Qiu2 1College of Pharmaceutical Sciences, 2Ministry of Education Key Laboratory of Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, People’s Republic of China Abstract: The use of vincristine (VCR) to treat cancer has been limited by its dose-dependent toxicity and development of drug resistance after repeated administrations. In this study, we investigated the mechanism by which quinine hydrochloride (QN) acts as a sensitizer for VCR. Our experiments used three kinds of multidrug-resistant cancer cells and demonstrated that QN worked by inducing intracellular depletion of adenosine triphosphate, increasing adenosine triphosphatase activity, and decreasing P-glycoprotein expression. Based on these results, we designed and prepared a VCR and QN codelivery liposome (VQL) and investigated the effect of coencapsulated QN on the in vitro cytotoxicity of VCR in cells and three-dimensional multicellular tumor spheroids. The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice. The results of this in vivo study indicated that VQL could reverse VCR resistance. In addition, it reduced tumor volume 5.4-fold when compared with other test groups. The data suggest that VQL could be a promising nanoscaled therapeutic agent to overcome multidrug resistance, and may have important clinical implications for the treatment of cancer. Keywords: vincristine, quinine, combination therapy, liposome, multidrug resistance reversal, P-glycoprotein
format	article
author	Xu YZ Qiu LY
author_facet	Xu YZ Qiu LY
author_sort	Xu YZ
title	Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
title_short	Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
title_full	Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
title_fullStr	Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
title_full_unstemmed	Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
title_sort	nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/ff77070bf7824804b1f21aa91db0d51b
work_keys_str_mv	AT xuyz nonspecificallyenhancedtherapeuticeffectsofvincristineonmultidrugresistantcancerswhencoencapsulatedwithquinineinliposomes AT qiuly nonspecificallyenhancedtherapeuticeffectsofvincristineonmultidrugresistantcancerswhencoencapsulatedwithquinineinliposomes
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Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes

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