Regulation effects and mechanism of liquiritin on immune function in gastric cancer-bearing mice
OBJECTIVE To study the regulation effects and mechanism of liquiritin(LIQ)on immune function in gastric cancer-bearing mice based on the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.METHODS Gastric cancer cells MFC were injected subcutaneously to establish gastric cancer-bearing model of mice.The model mice were divided into model group,LIQ low-dose group(LIQ-L group,20 mg/kg),LIQ high-dose group(LIQ-H group,40 mg/kg),and high-dose LIQ+JAK2 activator coumermycin A1 group(LIQ-H+coumermycin A1 group,40 mg/kg LIQ+1 mg/kg coumermycin A1),with 12 mice in each group.Another 12 mice without modeling were set as normal group.Mice in each group were given the corresponding drug or normal saline by intragastric administration/intraperitoneal injection,once a day,for consecutive 14 days.After the last administration,the volume and mass of gastric cancer tumor and organ index were measured.The percentages of CD4+and CD8+T lymphocytes were detected in peripheral blood.The histopathological morphology of gastric cancer tumor tissues was observed,and the expression levels of JAK2/STAT3 signaling pathway-related proteins and interleukin-6(IL-6)protein in gastric cancer tumor tissues were detected.RESULTS Compared with the normal group,the thymus index,spleen index,and the percentage of CD8+T lymphocyte in the peripheral blood of mice were obviously increased in model group(P<0.05),while the percentage of CD4+T lymphocyte in the peripheral blood were decreased(P<0.05).Compared with model group,the above indexes in LIQ-L group and LIQ-H group were significantly reversed(P<0.05),while the volume and mass of gastric cancer tumor,the phosphorylation levels of JAK2 and STAT3 protein and the expression level of IL-6 protein were significantly decreased in tumor tissue(P<0.05),and the effect of LIQ was in a dose-dependent manner(P<0.05);the tumor cells showed varying degrees of loose arrangement,vacuolization,and uneven distribution.JAK2 activator coumermycin A1 weakened the improvement effect of LIQ on the immune function of gastric cancer-bearing mice and its inhibitory effect on gastric cancer tumors(P<0.05).CONCLUSIONS LIQ can improve the immune function of gastric cancer-bearing mice by inhibiting the activation of JAK2/STAT3 signaling pathway,thus playing an anti-tumor role.
liquiritinJAK2/STAT3 signaling pathwaygastric cancerimmune function