Effects and mechanisms of saikosaponin D improving the sensitivity of human gastric cancer cells to cisplatin. - GreenMedInfo Summary

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 fromand exhibits various activities including antitumors. This study investigated the effects and the mechanisms of SSD on cisplatin (-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, IKKβ, p-IκBα, and NF-κB p65, suggesting that SSD might inhibit the IKKβ/NF-κB 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-κB 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 IKKβ/NF-κB pathway in GC cells. These findings suggested that SSD might contribute to overcoming DDP resistance in GC treatment.