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乐伐替尼调控VEGFR/NF-κB/R1P2信号治疗原发性肝细胞性肝癌的机制研究
作者:秦蜀  贺凯  李波  张孟瑜  冯春红  夏先明 
单位:西南医科大学附属医院 肝胆外科, 四川 泸州 646000
关键词:原发性肝细胞性肝癌 乐伐替尼 VEGFR/NF-κB/R1P2 
分类号:R735.7
出版年·卷·期(页码):2019·38·第一期(84-88)
摘要:

目的:探讨乐伐替尼调控VEGFR/NF-κB/R1P2信号治疗原发性肝细胞性肝癌的机制研究。方法:选取2016年5月至2017年10月本院收治的80例原发性肝细胞性肝细胞性肝癌患者接受口服乐伐替尼24 mg·d-1直至疾病恶化和出现无法耐受的毒副作用。评价药物使用疗效;采用免疫组织化学法检测患者癌组织中VEGFR2蛋白的表达;采用Real-Time PCR法和Western Blot法检测癌组织中NF-κB、R1P2、Bcl-2、Bcl-xl和Caspase-3的基因和磷酸化蛋白的表达。结果:乐伐替尼治疗原发性肝细胞性肝癌有效率为57.50%。与癌旁组织相比,原发性肝细胞性肝癌患者应用乐伐替尼治疗后,癌组织内NF-κB、R1P2、BCL-xl和Caspase-3 mRNA和蛋白表达明显上升,VEGFR2和BCL-2 mRNA和蛋白含量明显下降(P<0.05)。结论:乐伐替尼调控VEGFR/NF-κB/R1P2信号治疗原发性肝细胞性肝癌,促进肝细胞性肝癌细胞的凋亡。且不良反应发生率较低,临床应用安全性较高。

Objective:To study the mechanism of levotinib regulating VEGFR/NF-κB/R1P2 signaling in primary hepatocellular carcinoma. Methods:Eighty patients with primary liver cancer admitted to our hospital from March 2016 to October 2017 were enrolled in the study. The patients were treated with oral levoftenib 24 mg daily until the disease progressed and intolerance was unacceptable. Drug efficacy and adverse reactions were evaluated in patients; immunohistochemistry was used to detect the expression of VEGFR2 protein in cancer tissues; Real-Time PCR and Western Blot were used to detect NF-κB, R1P2, BCL-2, BCL-xl and Caspase3 mRNA expression and phosphorylated protein levels. Results:The effective rate of Lefatinib in the treatment of primary hepatocellular carcinoma was 57.50%. Compared with paracancerous tissues, the expression of NF-κB, R1P, BCL-xl, Caspase3 mRNA and protein in primary hepatocellular carcinoma was significantly increased, and the contents of VEGFR2, BCL-2 mRNA and protein were significantly decreased after lovastinib was treated with Lefatinib. The difference was statistically significant (P<0.05). Conclusion:Levitinib regulates the expression of VEGFR/NF-κB/R1P2 in hepatocellular carcinoma and promotes the apoptosis of hepatoma cells. The incidence of adverse reactions of levabinib in the treatment of primary liver cancer is low, and the clinical application is safe.

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