Anti-angiogenic efficacy of 5'-triphosphate siRNA combining VEGF silencing and RIG-I activation in NSCLCs.

// Dongmei Yuan 1, 2, * , Mao Xia 1, 4, * , Gang Meng 1 , Chun Xu 1 , Yong Song 2 , Jiwu Wei 1, 3 1 Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China 2 Department of Respiratory Medicine, Jinling Hospital, Nanjing, China 3 Nanjing University Hightech Institute at Suzhou, Suzhou, China 4 Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China * These authors have contributed equally to this work Correspondence to: Jiwu Wei, e-mail: wjw@nju.edu.cn Yong Song, e-mail: yong_song6310@yahoo.com Keywords: short interfering RNA, RIG-I, VEGF, NSCLC, anti-angiogenesis Received: April 29, 2015      Accepted: August 17, 2015      Published: August 27, 2015 ABSTRACT 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.