Effects and Mechanisms of Saikosaponin D Improving the Sensitivity of Human Gastric Cancer Cells to Cisplatin

Gastric cancer (GC) is the second leading cause of cancer deaths around the world. Chemoresistance is an important reason for poor prognosis of GC. Saikosaponin D (SSD) is a natural constituent from Radix Bupleuri and exhibits various activities including antitumors. This study investigated the effects and the mechanisms of SSD on cisplatin (cis-diamminedichloroplatinum, DDP) sensitivity of GC cells. Findings suggested that SSD could promote the inhibitory effect of DDP on proliferation and invasion and increase DDP-induced apoptosis in SGC-7901 and DDP-resistant cell line SGC-7901/DDP. We further identified that SSD increased levels of LC3 B and cleaved caspase 3 and decreased levels of p62, IKK beta, p-I kappa B alpha, and NF-kappa B p65, suggesting that SSD might inhibit the IKK beta/NF-kappa B pathway and induce both cell autophagy and apoptosis in SGC-7901 and SGC-7901/DDP. A further study indicated that SSD enhanced the effect of DDP-induced cleaved caspase 3 level rise and NF-kappa B pathway suppression, especially in SGC-7901/DDP cells. Conclusively, SSD enhanced DDP sensitivity of GC cells; the potential molecular mechanisms were that SSD-induced apoptosis and autophagy and inhibited the IKK beta/NF-kappa B pathway in GC cells. These findings suggested that SSD might contribute to overcoming DDP resistance in GC treatment.

Automated summary

Saikosaponin D (SSD) can enhance cisplatin sensitivity of gastric cancer cells by inducing apoptosis and autophagy, and inhibiting the IKK beta/NF-κB signaling pathway.