Liposomal simvastatin inhibits tumor growth via targeting tumor-associated macrophages-mediated oxidative stress

被引：65
作者：
Alupei, Marius Costel [1 ,2 ]
Licarete, Emilia [2 ]
Patras, Laura [1 ,2 ]
Banciu, Manuela [1 ,2 ]
机构：
[1] Univ Babes Bolyai, Fac Biol & Geol, Dept Mol Biol & Biotechnol, R-3400 Cluj Napoca, Romania
[2] Univ Babes Bolyai, Inst Interdisciplinary Res Bionanosci, Ctr Mol Biol, R-3400 Cluj Napoca, Romania
来源：
CANCER LETTERS | 2015年 / 356卷 / 02期
关键词：
Lipophilic statin; Liposomes; Cancer; Tumor-associated macrophages; Oxidative stress; NITRIC-OXIDE SYNTHASE; PREDNISOLONE PHOSPHATE; ANTITUMOR-ACTIVITY; BREAST-CANCER; B16; MELANOMA; HUMAN SERUM; EXPRESSION; HYPOXIA; STATINS; CARCINOMA;
D O I：
10.1016/j.canlet.2014.11.010
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Statins possess antitumor actions at doses 100- to 500-fold higher than those needed to lower cholesterol levels. Thus, the antitumor efficacy of statins could be improved greatly by using tumor-targeted delivery systems. Therefore the present work aims to investigate the antitumor activity of long-circulating liposome-encapsulated simvastatin (LCL-SIM) versus free SIM in B16.F10 murine melanoma-bearing mice. Our results showed that LCL-SIM inhibits strongly the B16.F10 melanoma growth (by 85%) whereas free SIM was ineffective. Moreover, the antitumor activity of LCL-SIM depends on the presence of functional tumor-associated macrophages (TAM) in tumor tissue and is mainly based on the reduction of the TAM-mediated oxidative stress as well as of the production of the hypoxia-inducible factor 1 alpha (HIF-1 alpha) in tumors. In conclusion, our findings suggest that the antitumor activity of LCL-SIM on B16.F10 melanoma growth is a result of the tumor-targeting property of the liposome formulation and is tightly dependent on the presence of TAM in tumor tissue. (C) 2014 Published by Elsevier Ireland Ltd.
引用
收藏
页码：946 / 952
页数：7
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