Liposomal curcumin inhibits Lewis lung cancer growth primarily through inhibition of angiogenesis

Abstract

Curcumin has been proven to effectively inhibit tumor growth by both targeting tumor cells and angiogenesis; however, poor water solubility limits further clinical application. In the present study, we prepared water-soluble liposomal curcumin to investigate its anti-tumor effects and the underlying mechanism. The MTT assay was used to test the anti-proliferative activities for the MS1 murine endothelial and LL/2 Lewis lung cancer cell lines. Apoptosis and cell cycle arrest induced by liposomal curcumin were analysed by flow cytometry. Anti-angiogenic agents and the resulting anti-tumor effects were investigated in a murine lung cancer model. Zebrafish were used to investigate the anti-angiogenic effect of liposomal curcumin in the development of embryos. In vitro, liposomal curcumin inhibited the proliferation of MS1 cells and induced cell cycle arrest and apoptosis. Notably, LL/2 cells showed less sensitivity to the liposomal curcumin in vitro. In vivo, the systemic administration of liposomal curcumin resulted in significant inhibition of tumor growth. CD31 immunohistochemical analysis and alginate encapsulation assay revealed that angiogenesis was decreased by liposomal curcumin treatment. Angiogenesis was also suppressed in the development of zebrafish. Liposomal curcumin showed potent inhibitory activity against murine endothelial cells but not lung cancer cells. Liposomal curcumin treatment is capable of significantly inhibiting tumor growth in vivo, a process that may depend primarily on its anti-angiogenic effects. Our study also indicates that liposomal curcumin may be developed not only for cancer therapy, but also for the treatment of other angiogenesis-related diseases.