Abstract

Background Worldwide, lung cancer is the most common cause of cancer-related deaths. Molecular targeted therapies and immunotherapies for non-small-cell lung cancer (NSCLC) have improved outcomes markedly over the past two decades. However, the vast majority of advanced NSCLCs become resistant to current treatments and eventually progress. A traditional Chinese medicine (TCM) formula of Shuangshen granules (SSG) has demonstrated potential in alleviating cancer side effects and improving survival rate. Despite clinical evidence supporting its benefit, there is still insufficient understanding of the active compounds in SSG and their underlying mechanisms, which limits its broader clinical application. Methods Lewis lung carcinoma (LLC) tumor-bearing mouse model was established to assess the efficacy of combined SSG and anti-PD-1 therapy in vivo, and myeloid-derived suppressor cells (MDSC) and CD8+T cells were isolated for in vitro co-culture experiments, while pathological examination was conducted using hematoxylin and eosin (HE). The expression of PD-1, TIM-3, CTLA-4, LAG-3, Arg-1, IDO, iNOS, PD-L1 and Gal-9 was detected using immunohistochemistry (IHC), immunofluorescence, and flow cytometry and Western blotting. The expression of IL-2, TNF-α and IFN-γ were detected by reverse transcription-quantitative polymerase chain reaction (qPCR). Concentrations of IL-10 and TGF-β were measured by enzyme-linked immunosorbent assay (ELISA). Network pharmacology and molecular docking were utilized to screen for potential therapeutic targets and intervening signaling pathways of SSG in lung adenocarcinoma (LUAD). The predictions derived from this approach were further verified using Western blotting. Results In vivo experiments using LLC xenograft mice demonstrated that SSG suppressed tumor growth in a dose-dependent manner, with high-dose SSG showing optimal efficacy in inhibiting tumor angiogenesis and cell proliferation.