Research Papers:

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

Dongmei Yuan _, Mao Xia, Gang Meng, Chun Xu, Yong Song and Jiwu Wei

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Oncotarget. 2015; 6:29664-29674. https://doi.org/10.18632/oncotarget.4869

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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

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


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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