苯基乙酰对小鼠移植性肺癌的抑制作用及其机制

摘要

目的 观察苯基乙酰(PG)对肺癌的抑制作用,并探讨其作用机制. 方法 选择C57BL/6小鼠40只,尾静脉注射肺癌LLC细胞建立肺癌模型. 随机将成模小鼠分为PG组、PBS组各20只,PG组腹腔内注射800 mg/kg PG, PBS组腹腔内注射等量PBS,连续10天. 两组各随机取5只,计数肺肿瘤个数、测量肿瘤最大直径;各随机取5只,采用Western blotting法观察肺癌组织Bcl-2、Bcl-XL、细胞凋亡抑制蛋白1(cIAP1)、Survivin、增殖细胞核抗原(PCNA)表达. 剩余小鼠收集支气管肺泡灌洗液( BALF) ,取5只小鼠的BALF,检测炎症细胞(包括WBC总数及分类)及炎症因子(TNF-α、IL-6、趋化因子);剩余小鼠的BALF,采用电泳迁移位移试验观察NF-κB DNA结合活力. 结果 与PBS组比较,PG组肺肿瘤个数和肿瘤最大直径明显减少或降低(P均<0.05). Western blotting结果显示,PG组Bcl-2、Bcl-XL、cIAP1、Survivin及PCNA表达均明显下调,BALF中巨噬细胞中NF-κB与靶DNA结合活性明显被抑制. 与PBS组比较,PG组可显著降低BALF中各种炎性细胞数量及炎症因子水平(P均<0.05). 结论 PG能明显抑制小鼠肺癌的生长,其机制与诱导肿瘤细胞凋亡、抑制巨噬细胞中NF-κB活性、减轻肺部炎症反应有关.%Objective To observe the inhibitory effect of phenylacetylglutamine ( PG) on lung caner and to investigate the mechanism.Methods The lung cancer metastasis models in C57BL/6 mice was generated by intravenous injection of Lewis lung carcinoma ( LLC) cells.Then the model mice were randomly divided into PG group ( n=20) which was injec-ted with 800 mg/kg PG and PBS group (n=20) which was injected with the same amount of PBS , both for 10 days.We randomly took 5 mice in each group to calculate the tumor count and measure the size of tumor .We randomly took 5 mice in each group to detect the expression of Bcl-2, Bcl-XL, cIAP1, Survivin and PCNA proteins by Western blotting .The broncho alveolar lavage fluid ( BALF ) from 5 mice were collected to detect inflammatory cells and inflammatory factors (TNF-α, IL-6, KC).The electrophoretic mobility shift assay (EMSA) was used to detect the NF-κB DNA binding abili-ty.Results Compared with the PBS group , the growth of lung tumors in mice was inhibited , and tumor number and tumor size decreased significantly in the PG group (P<0.05).The expression of Bcl-2, Bcl-XL, cIAP1, Survivin and PCNA was significantly decreased in the PG group .In BALF of the PG group, binding activity between NF-κB and target DNA was strongly suppressed .Compared with the PBS group , the number of BALF of various inflammatory cells and inflammato-ry cytokines were significantly reduced in the PG group (all P<0.05).Conclusion PG can inhibit the development of lung tumor, and the mechanism may be related with inducing lung tumor cell apoptosis , inhibiting the activation of NF-κB, and reducing the inflammatory reaction.