Anti-angiogenic efficacy of 5′-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs
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Dongmei Yuan1,2,*, Mao Xia1,4,*, Gang Meng1, Chun Xu1, Yong Song2, Jiwu Wei1,3
1Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
2Department of Respiratory Medicine, Jinling Hospital, Nanjing, China
3Nanjing University Hightech Institute at Suzhou, Suzhou, China
4Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
*These authors have contributed equally to this work
Jiwu Wei, e-mail: email@example.com
Yong Song, e-mail: firstname.lastname@example.org
Keywords: short interfering RNA, RIG-I, VEGF, NSCLC, anti-angiogenesis
Received: April 29, 2015 Accepted: August 17, 2015 Published: August 27, 2015
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.
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