Effect of Combination Use of Saikosaponin and PD-1/PD-L1 Inhibitor on Proliferation, Migration and Invasion of Gastric Cancer Cells and PI3K/AKT Signaling Pathway
Abstract: Objective: To observe the effect of the combination use of saikosaponin and programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor on proliferation, migration and invasion of gastric cancer cells and phosphatidylinositol 3-kinase/serine/threonine protein kinase( PI3K/AKT) signaling pathway. Methods: Human gastric cancer cells( BGC-803) were taken to culture in PD-1/PD-L1 inhibitor medium( PD-1/PD-L1 inhibitor group), saikosaponin medium (saikosaponin group), and PD-1/PD-L1 inhibitor combined with saikosaponin medium (combination group), and BGC-803 cells in the control group were cultured in serum-free medium. The viability of gastric cancer cells was detected; the proliferation rate, apoptosis rate, migration rate, invasion rate, levels of apoptosis-related proteins [Bcl-2-associated X protein (Bax),B-cell lymphoma-2 (Bcl-2),Caspase3 and Caspase8] and PI3K/AKT expression levels were compared among the four groups. Results:Saikosaponin could inhibit the growth of gastric cancer cells in a dose-dependent manner. The IC50 of saikosaponin on gastric cancer cells was 12.50 μg/mL. The proliferation rates, invasion rates, migration rates and the relative expression levels of Bcl-2, PI3K, p-PI3K, AKT and p-AKT in the PD-1/PD-L1 inhibitor group, the saikosaponin group and the combination group were reduced when compared with those in the control group (P<0.05),and the apoptosis rates and the relative expression levels of Bax, Caspase3 and Caspase8 were elevated (P<0.05). The proliferation rates, invasion rates, migration rates and the relative expression levels of Bcl-2, PI3K, p-PI3K, AKT and p-AKT in the PD-1/PD-L1 inhibitor group and the combination group were decreased when compared with those in the saikosaponin group (P< 0.05),and the apoptosis rates and the relative expression levels of Bax,Caspase3 and Caspase8 were increased (P< 0.05). The proliferation rates, invasion rates, migration rates and the relative expression levels of Bcl-2, PI3K,p- PI3K,AKT and p-AKT in the combination group were reduced when compared with those in the PD-1/PD-L1 inhibitor group (P<0.05), and the apoptosis rates and the relative expression levels of Bax, Caspase3 and Caspase8 were elevated (P<0.05). Conclusion:The intervention of saikosaponin combined with PD-1/PD-L1 inhibitor can inhibit the proliferation, migration, and invasion of gastric cancer cells and the activation of PI3K/AKT signaling pathway, and promote the apoptosis of gastric cancer cells.