Combination of DESI2 and IP10 gene therapy significantly improves therapeutic efficacy against murine carcinoma

作者: Chao Lin , HuaYing Yan , Jun Yang , Lei Li , Mei Tang

DOI: 10.18632/ONCOTARGET.17623

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摘要: // Chao Lin 1, * , HuaYing Yan 2, Jun Yang 1 Lei Li Mei Tang Xinyu Zhao Chunlai Nie Na Luo 3 Yuquan Wei and Zhu Yuan State Key Laboratory of Biotherapy, Collaborative Innovation Center West China Hospital, Chengdu, Sichuan University, 610041, 2 Department Functional Imaging, Provincial Women’s Children’s 610031, Nankai University School Medicine, Tianjin, 300071, These authors contributed equally to this work Correspondence to: Yuan, email: yuanzhu@scu.edu.cn Keywords: DESI2, IP10, apoptosis, anti-angiogenesis, antitumor immunity Received: December 23, 2016      Accepted: April 20, 2017      Published: May 05, 2017 ABSTRACT DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response DNA damage. We previously reported that overexpression induces S phase arrest apoptosis by activating checkpoint kinases. The present study was designed test whether combination IP10 could improve therapy efficacy in vitro vivo . recombinant plasmid co-expressing encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma LL2 lung cancer were treated complex. found that, more efficiently inhibited proliferation CT26, LL2, SKOV3 A549 cells via apoptosis. In combined significantly tumor growth prolonged survival mice. Mechanistically, augmented activity associated induction inhibition angiogenesis. anti-angiogenesis further mimicked inhibiting immortalized HUVEC Meanwhile, infiltration lymphocytes also enhanced effects. Depletion CD8+ T abrogated activity, whereas depletion CD4+ or NK showed partial abrogation. Our data suggest can enhance inducer, angiogenesis inhibitor immune initiator. may provide effective method for treating cancer.

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