Optimizing Component Formula Extracted from Ginseng and Salvia Inhibits Lung Cancer Metastasis and EMT via Suppressing AKT/GSK-3β/β-catenin Pathway

EMT plays a pivotal role in the metastatic progression of lung cancer. Ginseng and salvia are widely used combinations in Chinese medicine for cancer therapy, but its role in regulating cancer metastasis remained unknown. This investigation seeks to examine the efficacy and potential mechanism of optimizing component formula (OCF) extracted from ginseng and salvia on metastasis-associated EMT reprogramming in lung cancer. The inhibitory effects of OCF on tumor growth and metastatic cascades were systematically characterized in vitro . The tail vein injection method for lung metastasis model was used to observe anti-tumor metastasis effect of OCF in vivo . Molecular profiling involving PCRArray screening, quantitative PCR verification, and immunoblotting analysis elucidated the mechanistic basis. OCF markedly suppressed the proliferative capacity, migratory and invasive behavior in H1299 and 95D cells. Signal Transduction PathwayFinder PCRArray and qRT-PCR analysis confirmed that suppressing EMT was a potential way of OCF to inhibit metastasis in lung cancer. Mechanically, OCF exhibited a good affinity with AKT resulting in inhibition of the AKT/GSK-3β/β-catenin pathway. Co-treatment of OCF with SC79 or MK2206 demonstrated OCF weakened EMT progress via repressing AKT/GSK3β/β-catenin pathway in lung cancer. Furthermore, OCF treatment inhibited lung cancer growth and metastasis in vivo . Importantly, IHC and IF assays showed that OCF has also restrained the development of EMT and AKT/GSK3β/β-catenin pathway. OCF weakened EMT progression in lung cancer by suppressing AKT/GSK-3β/β-catenin pathway, which position OCF as a therapeutic candidate for lung cancer.