R424 – Suppression of HNSCC with Liposomal Curcumin and Cisplatin

Abstract

Problem To investigate whether curcumin, previously shown to inhibit growth of head and neck squamous cell carcinoma (HNSCC), can potentiate the anti-tumor effects of cisplatin in vitro and in vivo. Methods HNSCC cells were treated with curcumin and cisplatin, individually and together, and assayed for growth using MTT, western blotting, and immunofluorescence. Five-week old female athymic nude mice were utilized for in vivo experiments. HNSCC cells were injected to form xenograft tumors. Liposomal curcumin (50 ug/kg, maximum volume of 100ul) was administered intravenously three times per week for four weeks via tail vein injection. Mice were divided into three groups: no injection, liposomes alone, or liposomal cur-cumin. At the end of the fourth week, a single dose of intraperitoneal cisplatin was given to all groups. At the end of five weeks, the mice were euthanized and tumors were dissected and weighed. Results Addition of curcumin or cisplatin alone or in combination resulted in cell death. Introduction of suboptimal levels of both agents in vitro demonstrated a synergistic suppression of HNSCC cell line growth compared to individual agents. Xenograft tumors in nude mice treated with combination curcumin and cisplatin showed superior tumor growth suppression compared to control mice and mice treated with liposome alone. Average tumor size for mice treated with combination therapy was 30% smaller than controls. Conclusion Curcumin potentiates the anti-tumor activity of Cisplatin in vivo. Our data supports further investigation into the potential use of curcumin in combination with cisplatin in the treatment of HNSCC. Significance Current treatment modalities for HNSCC carry significant morbidity, which has led to the investigation of less toxic therapies. Previous studies by our group have demonstrated that liposome-encapsulated curcumin can suppresses growth of HNSCC. In this study, we assess the potential of combining liposomal curcumin with cisplatin in the treatment of HNSCC.