Antitumor and Antimetastatic Effect of Small Immunostimulatory RNA against B16 Melanoma in Mice

Tatyana O Kabilova; Aleksandra V Sen'kova; Valeriy P Nikolin; Nelly A Popova; Marina A Zenkova; Valentin V Vlassov; Elena L Chernolovskaya

doi:10.1371/journal.pone.0150751

Antitumor and Antimetastatic Effect of Small Immunostimulatory RNA against B16 Melanoma in Mice

PLoS One. 2016 Mar 16;11(3):e0150751. doi: 10.1371/journal.pone.0150751. eCollection 2016.

Authors

Tatyana O Kabilova¹, Aleksandra V Sen'kova¹, Valeriy P Nikolin², Nelly A Popova², Marina A Zenkova¹, Valentin V Vlassov¹, Elena L Chernolovskaya¹

Affiliations

¹ Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk, Russia, 630090.
² Institute of Cytology and Genetics SB RAS, 10, Lavrentiev Avenue, Novosibirsk, Russia, 630090.

Abstract

Small interfering RNAs, depending on their structure, delivery system and sequence, can stimulate innate and adaptive immunity. The aim of this study was to investigate the antitumor and antimetastatic effects of immunostimulatory 19-bp dsRNA with 3'- trinucleotide overhangs (isRNA) on melanoma B16 in C57Bl/6 mice. Recently developed novel cationic liposomes 2X3-DOPE were used for the in vivo delivery of isRNA. Administration of isRNA/2X3-DOPE complexes significantly inhibits melanoma tumor growth and metastasis. Histopathological analysis of spleen cross sections showed hyperplasia of the lymphoid white pulp and formation of large germinal centers after isRNA/2X3-DOPE administration, indicating activation of the immune system. The treatment of melanoma-bearing mice with isRNA/2X3-DOPE decreases the destructive changes in the liver parenchyma. Thus, the developed isRNA displays pronounced immunostimulatory, antitumor and antimetastatic properties against melanoma B16 and may be considered a potential agent in the immunotherapy of melanoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / pathology
Mice
Mice, Inbred C57BL
Neoplasm Metastasis / prevention & control*
RNA / therapeutic use*

Substances

RNA

Grants and funding

This research was supported by the Russian Academy of Science under the programs “Molecular and Cellular Biology” (no. 22-1), “Science to Medicine” (no. 44) and "Nanostructures: Physics, Chemistry, Biology, Technology"; by the Russian Foundation for Basic Research (no. 13-04-40181-H); by the grant of Scientific Schools (no. 1350.2014.4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.