Effects Of Propofol On Tumor Killing Activity Of Peripheral Blood NK Cells In Patients With Gastric Cancer After Operation

ObjectiveTo study the effect of propofol on the tumor killing activity of peripheral blood NK cells in patients with gastric cancer after surgery,and to preliminarily explore the molecular mechanism,so as to explore its clinical application value.MethodsThirty-six patients treated in our hospital who were clinically and pathologically diagnosed with gastric cancer were selected.Propofol was used for anesthesia induction and maintenance,and 5 ml of peripheral blood was collected at 1 h(T1)before anesthesia induction and at 24 h(T2)after operation respectively,freshly resected tumor tissues and corresponding adjacent tissues were collected after operation.Natural killer cells(NK)were purified by magnetic beads and co-cultured with gastric cancer cells BGC-823 to observe the apoptosis rate of T1 and T2 peripheral blood NK cells on human gastric cancer cells.The expression of granulase B(GZMB),factor-interferon(IFN-γ),and Perforin(PFP)was analyzed by flow analysis.NK cells isolated and purified from normal healthy volunteers were co-cultured with BGC-823 culture supernatant to observe the tumor-killing ability and GZMB expression of NK cells.Propofol was added to observe the effect of propofol on the tumor killing function of NK cells and the expression capacity of GZMB.On this basis,transforming growth factor(TGF-β1)was added to observe the tumorkilling ability of propofol on NK cells and the recovery effect of GZMB.Western blot was used to detect the expression of SMAD4 protein in NK cells,interfere with the expression of SMAD4,observe the NK cells killing activity and the change of GZMB expression,and observe the recovery effect of propofol.Results1.The tumor killing activity of peripheral blood NK cells was higher than that of T1 at T2(P<0.05).2.The expression of effector GZMB in NK cells increased(P<0.05).3.The supernatant of gastric cancer cells BGC-823 could inhibit the tumor killing activity of NK cells and down-regulate the expression of GZMB(P<0.05).4.After the addition of propofol and TGF-β1 antibody,the tumor killing ability and GZMB expression of gastric cancer cells in supernatant culture of BGC-823 significantly recovered.In terms of mechanism,after the addition of propofol and TGF-β1 antibodies,the nuclear translocation of SMAD4 protein in NK cells after co-culture was significantly higher than that of the BGC-823 co-culture group.After interfering with the expression of SMAD4 in NK cells,the promoting effect of propofol on the expression of GZMB in NK cells was significantly inhibited(P<0.05).ConclusionsThe tumor killing activity of peripheral blood NK cells in patients with gastric cancer was significantly reduced compared with that in healthy people,and propofol induced anesthesia could promote the tumor killing activity of peripheral blood NK cells in patients with gastric cancer.Propofol regulates the expression of GZMB in NK cells through the SMAD4 signaling pathway,thereby affecting its function.