Abstract:
Objective To explore the effects of remifentanil on the proliferation, cycle and apoptosis of hepatocellular carcinoma cells as well as the related Notch signaling pathway.
Methods Hepatocellular cancer cells HepG2 were cultured in vitro and treated with remifentanil at different concentrations (0, 5, 50, 500 ng/mL), which were recorded as the remifentanil dose groups. Cells were treated with 500 ng/mL remifentanil and 20 μmol/L Notch pathway inhibitor DAPT, which were named as remifentanil group and remifentanil+DAPT group respectively. CCK8 was used to detect cell proliferation; flow cytometry was used to detect cell cycle and apoptosis; western blot was used to detect the expressions of p27, Cyclin D1, Bax, cleaved cas-3, and Notch pathway related proteins.
Results Remifentanil at concentrations of 0, 5, 50 and 500 ng/mL could reduce the optical density value at 450 nm (OD450 nm value) and S stage cell ratio, increase the G0/G1 stage cell ratio and apoptosis rate, up regulate the expressions of p27, Bax and cleaved CAS-3 proteins, and downregulate the expressions of Cyclin D1, Notch1 and Hes1 proteins in a concentration dependent manner. The OD450 nm value, S stage cell ratio and expression of Cyclin D1 protein in remifentanil+DAPT group were significantly lower than those in remifentanil group, and the G0/G1 stage cell ratio, apoptosis rate, and expressions of p27, Bax and cleaved CAS-3 proteins were significantly higher than those in remifentanil group (P < 0.05).
Conclusion Remifentanil can inhibit the proliferation of hepatocarcinoma cells, block cell cycle, induce apoptosis and inhibit Notch signaling pathway.