Kabilova Tatyana O, Sen'kova Aleksandra V, Nikolin Valeriy P, Popova Nelly A, Zenkova Marina A, Vlassov Valentin V, Chernolovskaya Elena L
Institute of Chemical Biology and Fundamental Medicine SB RAS, 8, Lavrentiev Avenue, Novosibirsk, Russia, 630090.
Institute of Cytology and Genetics SB RAS, 10, Lavrentiev Avenue, Novosibirsk, Russia, 630090.
PLoS One. 2016 Mar 16;11(3):e0150751. doi: 10.1371/journal.pone.0150751. eCollection 2016.
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.
小干扰RNA根据其结构、递送系统和序列的不同，可刺激先天性免疫和适应性免疫。本研究旨在探讨具有3' - 三核苷酸突出端的免疫刺激性19碱基对双链RNA（isRNA）对C57Bl/6小鼠黑色素瘤B16的抗肿瘤和抗转移作用。最近开发的新型阳离子脂质体2X3 - DOPE被用于isRNA的体内递送。给予isRNA/2X3 - DOPE复合物可显著抑制黑色素瘤肿瘤生长和转移。脾脏横断面的组织病理学分析显示，给予isRNA/2X3 - DOPE后，淋巴白髓增生并形成大的生发中心，表明免疫系统被激活。用isRNA/2X3 - DOPE治疗荷黑色素瘤小鼠可减少肝实质的破坏性变化。因此，所开发的isRNA对黑色素瘤B16显示出显著的免疫刺激、抗肿瘤和抗转移特性，可被认为是黑色素瘤免疫治疗的潜在药物。
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