Ketamine exhibits anti-gastric cancer activity via induction of apoptosis and attenuation of PI3K/Akt/mTOR.

Abstract

IntroductionGastric cancer (GC) is the most widespread type of cancer after lung and liver cancer in men and after breast cancer in women. Thus, the present study was intended to evaluate the effect of ketamine (KET) on gastric cancer cells.Material and methodsThe effect of KET was analyzed in vitro by the MTT assay against human gastric cancer cell lines BGC-823, MKN-45 and MKN-28. The effect KET on apoptosis, cell migration and cell cycle arrest was also quantified. Western blot analysis was performed to estimate the effect of KET on apoptosis mediators and PI3K/AKT/mTOR pathway mediators. A mouse xenograft assay was also conducted to further confirm the anticancer activity.ResultsKET causes reduction of cellular viability of BGC-823, MKN-45 and MKN-28, with a more significant effect against BGC-823 cells. The KET treatment showed a dose-dependent increase in apoptotic cells among BGC-823 cells. KET causes a significant dose-dependent decline in migration of treated cells. It causes induction of apoptosis mediated via the mitochondrial pathway, where it causes a decline in Bcl2 and mitochondrial cytochrome c level together with increase in expression of Bax, cytosolic cytochrome c and cytosolic apoptotic protease activating factor-1 (Apaf-1). The level of p-PI3K, p-mTOR, p-GSK3β and p-AKT was found to be downregulated in a dose-dependent manner in KET-treated cells. In a mouse xenograft model, KET causes a reduction in relative tumour volume and tumour weight.ConclusionsOur results suggest that ketamine has the ability to inhibit progression of gastric cancer via induction of apoptosis and attenuation of PI3K/Akt/mTOR.