顺铂联合异甘草酸镁对原发性肝癌小鼠疾病进展影响及相关机制研究

Effects of Cisplatin Combined with Magnesium Isoglycyrrhizinate on the Progress in Mice with Primary Hepatocellular Carcinoma and Its Mechanism

关键词:  顺铂  异甘草酸镁  原发性肝癌

Key words:  cisplatin  magnesium isoglycyrrhizinate  primary liver cancer

摘要:

目的 了解顺铂联合异甘草酸镁调控ERK1/2信号通路干预原发性肝癌小鼠疾病进展及对PGE2及γδT细胞表达水平的影响。方法 建立45只原发性肝癌小鼠模型，随机分为对照组、顺铂组、联合用药组，各15只，分别腹腔注射给予生理盐水、顺铂、顺铂联合异甘草酸镁。比较其治疗效果，血清肝功能指标，前列腺素E2（prostaglandin E2，PGE2）水平，肝脏核因子-κB（nuclear factor-κB，NF-κB）p65和炎症因子表达，细胞外调节蛋白激酶1/2（extracellular regulated protein kinases，ERK1/2）及p-ERK1/2蛋白相对表达量，γδT细胞百分比。结果 联合用药组肿瘤质量最低，顺铂组肿瘤质量较联合用药组高，对照组最高（P<0.05）；联合用药组抑瘤率大于顺铂组（P<0.05）；联合用药组血清丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转氨酶（aspartate aminotransferase，AST）、PGE2水平、肝脏肿瘤坏死因子、血管内皮生长因子、NF-κB p65蛋白量最低，顺铂组较联合用药组高，对照组最高（P<0.05）；3组肝脏ERK1/2蛋白相对表达量无差异；联合用药组肝脏p-ERK1/2蛋白相对表达量、γδT细胞百分比最低，顺铂组较联合用药组高，对照组最高（P<0.05）。结论 顺铂联合异甘草酸镁可调控ERK1/2及NF-κB信号通路从而干预原发性肝癌小鼠疾病进展，并且可降低γδT细胞百分比，调节免疫机能。

Abstract:

OBJECTIVE To know the effects of cisplatin combined with magnesium isoglycyrrhizinate on the intervention of progress in mice with primary hepatocellular carcinoma through ERK1/2 signaling pathway and the expression of PGE2 and γδT cells. METHODS Forty-five model mice with primary liver cancer were established and randomly divided into control group, cisplatin group and combined treatment group, each with 15 mice. Normal saline, cisplatin and cisplatin combined with magnesium isoglycyrrhizinate were given intraperitoneally respectively. The therapeutic effects, serum liver function index, prostaglandin E2(PGE2) level, liver nuclear factor-κB(NF-κB) p65, inflammatory factor expression, relative expression of protein on extracellular regulated protein kinases1/2(ERK1/2) and p-ERK1/2, percentage of γδT cells were compared in them. RESULTS The quality of tumor in combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). The tumor inhibition rate in the combination group was higher than the cisplatin group(P<0.05). The levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) and PGE2, protein of liver tumor necrosis factor-α(TNF-α), vascular endothelial growth factor(VEGF), NF-κB p65 in the combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). There was no difference in the relative protein expression of ERK1/2 among the three groups. The relative expression of p-ERK1/2 protein in live, percentage of γδT cells in the combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). CONCLUSION Cisplatin combined with magnesium isoglycyrrhizinate can regulate the ERK1/2 and NF-κB signaling pathway and interfere with the progression of primary liver cancer in mice. It can also reduce the percentage of γδT cells and regulate immune function.