Journal Title
Title of Journal: Drug Deliv and Transl Res
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Abbravation: Drug Delivery and Translational Research
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Authors: Anubhab Mukherjee Jayanta Bhattacharyya Madamsetty Vijay Sagar Arabinda Chaudhuri
Publish Date: 2013/03/23
Volume: 3, Issue: 3, Pages: 224-234
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 19bp 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 19bp 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 growthThis work was supported by the Council of Scientific and Industrial Research CSIR Government of India New Delhi NWP0036 and CSC0302 AM JB and MVS thank the Council of Scientific and Industrial Research Government of India New Delhi for the doctoral research fellowships
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