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.
Keywords: DC; PI3K/Akt/p53; PolyI:C; TLR3; cytokines; immunotherapy; lung cancer.