Anti-tumor outcome evaluation against non-small cell lung cancer in vitro and in vivo using PolyI:C as nucleic acid therapeutic agent

American Journal of Translational Research

Yedan Wu¹  Wei Huang²  Liqing Chen³ 

[1] Department of Respiratory Medicine, Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China;State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;Xinfu (Beijing) Pharmaceutical Technology Co., Ltd, Beijing 100085, China

关键词: TLR3;    PolyI:C;    lung cancer;    immunotherapy;    PI3K/Akt/p53;    cytokines;    DC;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

PolyI:C as a ligand of toll-like receptor 3 has been explored as a nucleic acid therapeutic agent for anti-tumor therapy. The previous PolyI:C studies mainly focused on anti-tumor evaluation at cell level and anti-tumor mechanism involved in MyD88-independent pathway. However, there is a lack of information about the ability of PolyI:C to affect PI3K/Akt/p53 signaling pathway in non-small cell lung cancer (NSCLC), and its pharmacodynamic evaluation in vivo still remain unclear so far. In this study, we explored the anti-tumor mechanism and efficacy in vivo of PolyI:C in NSCLC. Our results showed that PolyI:C had the ability to inhibit tumor cell proliferation and promote cell apoptosis by inducing G1 cell cycle block in LL/2 and A549 NSCLC cells. In vivo animal studies also demonstrated that PolyI:C effectively inhibited the tumor growth, suppressed spontaneous metastasis and prolonged the survival time of LL/2 tumor-bearing mice. Moreover, western blotting and immunohistochemistry assays showed that its anti-tumor mechanism was associated with the interference with PI3K/Akt/p53 signaling pathway. Our results confirmed that PolyI:C increased the expression of CD80, CD86 in spleen dendritic cells of tumor-bearing mice and cytokine secretion in healthy mice. Generally, our study suggests that PolyI:C can become a promising anti-tumor agent.

【 授权许可】

CC BY-NC