Abstract

Purpose To investigate the potential biomarkers, key metabolic pathways, and regulatory mechanisms of Fan Bei San Jie Capsule (FBSJC) in the treatment of lung cancer. Methods In this study, we utilized high-performance liquid chromatography mass spectrometry to identify the pharmaceutical constituents of FBSJC. Firstly, we established a subcutaneous tumor transplantation model in nude mice to evaluate the inhibitory effect of FBSJC on tumor growth. On this basis, we applied metabolomics to investigate the differential genes and downstream signaling pathways associated with FBSJC. The potential mechanism underlying the anti-tumor effect of FBSJC was further investigated through in vivo and in vitro experiments. We conducted pathological experiments, including HE staining, immunohistochemistry, and TUNEL assays, as well as cellular experiments such as CCK8, apoptosis, Transwell, and scratch assays, along with Western blot analyses. Results The experimental results indicated that a total of 1,162 compounds were present in FBSJC. We identified the target SPHK1 and the metabolic pathway involving JAK2/ERK through KEGG enrichment and pathway analysis. The results of both in vitro and in vivo experiments demonstrated that FBSJC inhibited lung cancer by downregulating SPHK1 protein expression and activating the downstream JAK2/ERK signaling pathway. Overexpression of SPHK1 promoted the proliferation of lung cancer cells, inhibited apoptosis, upregulated S1PR1 and HIF-1, and enhanced the phosphorylation of ERK1/2 and JAK2. This process attenuated the cancer-inhibitory effects of FBSJC. Conclusion FBSJC inhibits the progression of lung cancer and is associated with the suppression of SPHK1-mediated activation of the JAK2/ERK signaling pathway.