Small interfering RNA (siRNA)-mediated knockdown of Notch1 suppresses tumor growth and enhances the effect of IL-2 immunotherapy in malignant melanoma.

ABSTRACT

PURPOSE: Malignant melanoma (MM) is a highly aggressive neoplasm that is resistant to conventional therapies. In this study, we aimed to investigate the effects of antitumor and immune enhancement of Notch1 knockdown on MM. METHODS: Mouse melanoma cells B16F1 were transfected with a small interfering RNA (siRNA) targeting Notch1 (siNotch1). RESULTS: The expression of Notch1 and its downstream hey1 was significantly decreased, resulting in reduced cell proliferation in vitro. Furthermore, intratumoral injection of siNotch1 successfully inhibited the expression of Notch1 and hey1, which suppressed tumor growth, and increased the number of tumor-infiltrating CD8+ T lymphocytes and IFN-γ secretion in vivo, especially when combined with IL-2 immunotherapy. CONCLUSION: These results suggested that siRNA-mediated Notch1 knockdown might be an effective method for the inhibition of tumor growth both in vivo and in vitro, and might potentially enhance the effect of IL-2 immunotherapy in MM. Notch1 knockdown concurrently administered with IL-2 might be a novel therapeutic approach for the treatment of MM.