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Published on: November 1, 2017
Liposomal simvastatin inhibits tumor growth via targeting tumor-associated macrophages-mediated oxidative stress
Marius Costel Alupei1, Emilia Licarete2, Laura Patras1
1Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, Babes-Bolyai University, Cluj-Napoca, Romania; Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, Babes-Bolyai University, Cluj-Napoca, Romania.
Abstract:
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 α (HIF-1 α) 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.
Insights
Long-circulating liposome-encapsulated simvastatin (LCL-SIM) effectively inhibited melanoma growth by 85% in mice. This antitumor effect relies on tumor-associated macrophages (TAM) and reduced oxidative stress.
Area of Science:
- Oncology
- Pharmacology
- Nanomedicine
Background:
- Statins exhibit antitumor properties at high doses, necessitating improved delivery for efficacy.
- Tumor-targeted delivery systems can enhance the therapeutic potential of statins.
Purpose of the Study:
- To evaluate the antitumor activity of liposome-encapsulated simvastatin (LCL-SIM) compared to free simvastatin (SIM) in a B16.F10 murine melanoma model.
- To elucidate the mechanisms underlying LCL-SIM's antitumor effects, focusing on tumor-associated macrophages (TAM) and related pathways.
Main Methods:
- Administration of LCL-SIM and free SIM to B16.F10 melanoma-bearing mice.
- Assessment of tumor growth inhibition.
- Analysis of TAM function, oxidative stress, and hypoxia-inducible factor 1 α (HIF-1 α) levels within tumors.
Main Results:
- LCL-SIM significantly inhibited B16.F10 melanoma growth by 85%, while free SIM showed no significant effect.
- The antitumor activity of LCL-SIM was dependent on the presence of functional TAM.
- LCL-SIM reduced TAM-mediated oxidative stress and HIF-1 α production in tumors.
Conclusions:
- Liposome encapsulation enhances simvastatin's antitumor efficacy through tumor targeting.
- The mechanism involves TAM modulation, reduction of oxidative stress, and decreased HIF-1 α.
- LCL-SIM represents a promising strategy for melanoma treatment, contingent on TAM presence.
