A TCM Formula YYWY Inhibits Tumor Growth in Non-Small Cell Lung Cancer and Enhances Immune-Response Through Facilitating the Maturation of Dendritic Cells

In worldwide, lung cancer has a major socio-economic impact and is one of the most common causes of cancer-related deaths. Current therapies for lung cancer are still quite unsatisfactory, urging for alternative new treatments. Traditional Chinese Medicine (TCM) is currently increasingly popular and exhibits a complicated intervention in cancers therapy. In this study, we evaluated the anti-tumor effect and explored the mechanisms of a TCM formula Yangyinwenyang (YYWY) in non-small cell lung cancer (NSCLC) models. YYWY induced the apoptosis of lung cancer cells in vitro. In Lewis NSCLC-bearing mice model, YYWY significantly inhibited the tumor growth. Further, RNA-seq analysis and immunostaining of the tumor tissue implied the critical role of YYWY in the regulation of immune response, especially the dendritic cells (DCs) in the effect of YYWY. Therefore, we focused on DCs, which were the initiator and modulator of the immune response. YYWY facilitated the maturation of DCs through MAPK and NF-κB signaling pathways and promoted the release of the cytokines IFN-γ, interleukin (IL)-1β, IL-2, IL-12, and tumor necrosis factor (TNF)-α by DCs. Moreover, the YYWY-matured DCs enhanced the proliferation of T cells and promoted the differentiation of T cells into T helper Th1 and cytotoxic T cell (CTL). In addition, YYWY increased the ratio of Th1/Th2 (IFN-γ/IL-4 radio). Collectively, our findings clearly suggested that YYWY exerted an anti-tumor effect on NSCLC, at least partially through facilitating the mature DCs to activate the proliferation and differentiation of T cells.