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

Abstract

Introduction: Gastric 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 methods: The 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. Results: KET 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. Conclusions: Our results suggest that ketamine has the ability to inhibit progression of gastric cancer via induction of apoptosis and attenuation of PI3K/Akt/mTOR.

Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme

“…Numerous studies have indicated that ketamine exerts potential pharmacological effects, including apoptosis and autophagy induction, attenuation of PI3K/Akt/mammalian target of rapamycin (mTOR), increase in eNOS gene expression, and blockage of NMDA receptor against various tumoral cell lines (Duan et al , 2019, Yuhas et al , 2017, Zhao et al , 2019, Zhou et al , 2018. As mentioned earlier, SP was shown to cause the release of pro-inflammatory cytokines mediated by the NK-1R in the pathogenesis of many human brain disorders (Martinez et al , 2016).…”

MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer

“…In research on many anti-cancer drugs, the MAPK/mTOR/p70S6K and Akt pathways or the PI3k-Akt pathway are involved in the regulation of pAKT expression and contribute to inhibition of tumor growth [ 75 , 76 , 77 , 78 ]. pAMPK is also one of the proteins involved in proliferation and apoptosis of gastric cancer cells.…”

Ellagic acid inhibited cervical cancer growth via blocking the AKT/mTOR/STAT3 pathway

“…The proliferation, migration and invasion of cells are closely related to the progress of tumor, so inhibiting the growth and migration of tumor cells may be an important means to prevent tumor progression [26]. HeLa cell activity enhancement (proliferation, invasion and migration) plays an important role in the occurrence and development of cervical cancer.…”