Effects of low-dose naloxone combined with morphine on tumor microenvironment in lung cancer tumor-bearing mice
Objective To observe the effect of low-dose naloxone combined with morphine on the tumor microenvironment of lung tumor-bearing mice.Methods To established a lung tumor-bearing mouse model and randomly divided 24 mice into four groups:model group(group A),naloxone group(group B),morphine group(group C),and naloxone combined with morphine group(Group D),with 6 in each group.After tumor formation,group A was injected with 100 μl of normal saline subcutaneously at the back of the neck;group B was injected with naloxone 0.357 mg/kg subcutaneously at the back of the neck;group C was injected with morphine 0.357 mg/kg subcutaneously at the back of the neck;group D was injected naloxone 0.357 mg/kg+morphine 0.357 mg/kg subcutaneously with the back of the neck.2 times a day,continuous injection for 14 days.The long and short diameters of the tumor were measured every three days,calculated the relative volume of the tumor(RTV).The level of mouse tumor necrosis factor(TNF-α),mouse interleukin 10(IL-10),changes in mouse gamma interferon(IFN-γ),mouse β-endorphin(β-EP),and mouse glutamine(Gln)were detected by ELISA kit.The expressions of CD4,CD8 and CD158 were detected by immunohistochemistry.The expression of Bcl-2,MOR,OGFR,and PD-1 in tumor tissues was detected by the Western blot method.Results Low-dose naloxone combined with morphine group can inhibit RTV;the levels of IL-10 and β-EP in serum of mice in naloxone combined with morphine group were significantly lower than those in model group.The expression of CD4,CD158 protein in tumor-bearing tissues of mice in naloxone combined with morphine group were higher than that in model group,and the expression of PD-1,MOR、Bcl-2 and was significantly lower than that in model group.Conclusion Low-dose naloxone combined with morphine can improve the tumor microenvironment,and its mechanism may be related to up-regulating the expression of CD4,CD158 and down-regulating the expression of PD-1,MOR,Bcl-2.
万方数据
维普
