ETHNOPHARMACOLOGICAL RELEVANCE:The Shenlingcao oral liquid (SLC), derived from traditional clinical formulations, can enhance physical strength and vitality during chemotherapy for malignant tumors. Previous studies have indicated that SLC can enhance the quality of life and daily functioning of patients with non-small cell lung cancer (NSCLC) within 6 months after adjuvant chemotherapy following radical surgery. Nevertheless, its precise mechanism of action is unclear.
AIM OF THE STUDY:To elucidate the function and underlying mechanism of SLC in enhancing the effect of cisplatin in treating NSCLC.
MATERIALS AND METHODS:UPLC-Q-Exactive Plus-MS/MS was used to characterize the chemical constituents of SLC. The main gene targets and the pathways of SLC that impact NSCLC were predicted using network pharmacology. A mouse model of Lewis lung cancer and the combination of transcriptomics, metabolomics, and 16S rRNA analysis were used to investigate the underlying mechanisms of the SLC-cisplatin combination in influencing the pathology of NSCLC.
RESULTS:The SLC-cisplatin combination significantly reduced tumor volume and weight (P < 0.01), boosted T lymphocytes (P < 0.05), increased cleaved-caspase-3/caspase-3 expression (P < 0.05), and decreased p-PI3K/PI3K, p-AKT/AKT, and Bcl-2/Bax protein levels (P < 0.05) compared with cisplatin monotherapy. It also improved the gut flora by enriching the abundance of Bacteroidaceae, S24-7, and Porphyromonadaceae, while modulating metabolic pathways, including caffeine metabolism and fatty acid degradation.
CONCLUSIONS:SLC enhanced the effect of cisplatin in inhibiting NSCLC by inducing cell apoptosis, augmenting immune responses, balancing the gut microbiota, and regulating key metabolic pathways. Our findings highlight the potential of SLC as an effective adjuvant therapy for NSCLC.