Liposomally encapsulated CDC20 siRNA inhibits both solid melanoma tumor growth and spontaneous growth of intravenously injected melanoma cells on mouse lung

Abstract

Cell division cycle homologue 20 (CDC20), a key cell cycle regulator required for the completion of mitosis in organisms from yeast to human, is highly expressed in several carcinomas. Recent studies have shown that specific knockdown of CDC20 expression is capable of significantly inhibiting the growth of human pancreatic carcinoma cells. However, preclinical studies aimed at demonstrating the therapeutic potential of CDC20 siRNA in combating tumor growth has not yet been reported. Herein, in a syngeneic C57BL/6J mouse tumor model, we show that intraperitoneal administration of a 19-bp synthetic CDC20 siRNA encapsulated within liposomes of guanidinylated cationic amphiphile with stearyl tails inhibits solid melanoma (B16F10) tumor growth. In addition, using a spontaneous lung metastasis model in C57BL/6J mice, we show that intravenous administration of the same liposomally encapsulated 19-bp synthetic CDC20 siRNA inhibits B16F10 melanoma growth on mouse lung. Liposomally bound CDC20 siRNA was found to be efficient in silencing the expression of CDC20 in B16F10 cells at both protein and mRNA levels. Findings in the flow cytometric studies confirmed the presence of significantly enhanced populations of G2/M phase in cells treated with liposomally bound CDC20 siRNA. To the best of our knowledge, the present findings demonstrate, for the first time, systemic use of CDC20 siRNA in inhibiting mouse tumor growth.