Sinigrin inhibits PD-L1 expression via suppressing the JAK-STAT signaling pathway to modulate the tumor immune microenvironment in lung cancer.

Lung cancer is one of the most common malignant tumors worldwide. During the development and progression of lung cancer, the increase in PD-L1 expression inhibits T cell activity, leading to an immunosuppressive tumor microenvironment. Sinigrin (Sin) is a natural aliphatic glucoside with various pharmacological effects such as anti-cancer and immunomodulation. However, its role in lung cancer and the underlying mechanism remain unclear. This study aims to explore the therapeutic potential and molecular mechanism of sinigrin in improving the immune microenvironment of lung cancer. Experiments conducted in vitro demonstrated that sinigrin can effectively inhibit the viability, proliferation and migration of cancer cells, promote their apoptosis, and significantly reduce the expression level of PD-L1. Moreover, the effect of sinigrin on cancer cells is dose-dependent. The results of in vivo experiments indicated that sinigrin can effectively inhibit tumor growth and proliferation, promote tumor cell apoptosis, suppress the expression of PD-L1, enhance T-cell activation, and improve the tumor immune microenvironment. Network pharmacology and in vitro experimental analyses revealed that sinigrin exerts its therapeutic effect by inhibiting the expression of PD-L1 through the JAK/STAT signaling pathway. Sinigrin inhibits the expression of PD-L1 by suppressing the JAK-STAT signaling pathway, thereby improving the immune microenvironment of lung cancer and providing an effective therapeutic strategy for blocking the progression of lung cancer.