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

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...

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Bibliographic Details
Published in:PloS one 2016-03, Vol.11 (3), p.e0150751-e0150751
Main Authors: Kabilova, Tatyana O, Sen'kova, Aleksandra V, Nikolin, Valeriy P, Popova, Nelly A, Zenkova, Marina A, Vlassov, Valentin V, Chernolovskaya, Elena L
Format: Article
Language:English
Subjects:
Acids
Adaptive immunity
Adaptive systems
Animals
Anticancer properties
Antigens
Antitumor activity
Biology and Life Sciences
Cancer therapies
Care and treatment
Cellular biology
Cytokines
Dendritic cells
Double-stranded RNA
Genetic aspects
Germinal centers
Hyperplasia
Immune system
Immunity
Immunostimulation
Immunotherapy
Interferon
Kinases
Laboratory animals
Ligands
Liposomes
Liver
Medicine
Medicine and Health Sciences
Melanoma
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
Metastases
Metastasis
Mice
Mice, Inbred C57BL
Neoplasm Metastasis - prevention & control
Parenchyma
Pulp
Ribonucleic acid
RNA
RNA - therapeutic use
Skin cancer
Spleen
Tumors
White pulp
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0150751