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

Drug Delivery and Translational Research volume 3, pages 224–234 (2013)Cite this article

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.

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Acknowledgments

This work was supported by the Council of Scientific and Industrial Research (CSIR), Government of India, New Delhi (NWP-0036 and CSC0302). A.M., J.B., and M.V.S. thank the Council of Scientific and Industrial Research, Government of India, New Delhi for the doctoral research fellowships.

Integrity of research and reporting

The experiments described in this manuscript comply with the current laws of India.

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Author notes

  1. Jayanta Bhattacharyya

    Present address: Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, NC, 27708-0271, USA

Affiliations

  1. Division of Lipid Science and Technology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Anubhab Mukherjee, Jayanta Bhattacharyya, Madamsetty Vijay Sagar & Arabinda Chaudhuri

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  1. Anubhab Mukherjee
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  2. Jayanta Bhattacharyya
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Correspondence to Arabinda Chaudhuri.

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Authors Anubhab Mukherjee and Jayanta Bhattacharyya contributed equally to this work.

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Mukherjee, A., Bhattacharyya, J., Sagar, M.V. et al. Liposomally encapsulated CDC20 siRNA inhibits both solid melanoma tumor growth and spontaneous growth of intravenously injected melanoma cells on mouse lung. Drug Deliv. and Transl. Res. 3, 224–234 (2013). https://doi.org/10.1007/s13346-013-0141-3

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  • DOI: https://doi.org/10.1007/s13346-013-0141-3

Keywords

  • Systemic RNAi
  • Melanoma growth inhibition
  • CDC20 siRNA
  • Inhibition of mitosis
  • Cationic transfection lipids