Anti-angiogenic efficacy of 5'-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs.
Short interfering RNA (siRNA) targeting angiogenic factors and further inhibiting tumor angiogenesis, is one of the potent antitumor candidates for lung cancer treatment. However, this strategy must be combined with other therapeutics like chemotherapy. In this study, we designed a 5'-triphosphate siRNA targeting VEGF (ppp-VEGF), and showed that ppp-VEGF exerted three distinct antitumor effects: i) inhibition of tumor angiogenesis by silencing VEGF, ii) induction of innate immune responses by activating RIG-I signaling pathway, and thus activate antitumor immunity, iii) induction of apoptosis. In a subcutaneous model of murine lung cancer, ppp-VEGF displayed a potent antitumor effect. Our results provide a multifunctional antitumor molecule that may overcome the shortages of traditional antiangiogenic agents.
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|Department of Respiratory Medicine, Jinling Hospital, Nanjing, China.
Dongmei
D
Yuan
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
Mao
M
Xia
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
Gang
G
Meng
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
Chun
C
Xu
Department of Respiratory Medicine, Jinling Hospital, Nanjing, China.
Yong
Y
Song
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.|Nanjing University Hightech Institute at Suzhou, Suzhou, China.
Jiwu
J
Wei
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011122:Polyphosphates / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D007370:Interferon Type I; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011122:Polyphosphates; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid
NSCLC; RIG-I; VEGF; anti-angiogenesis; short interfering RNA