二去水卫矛醇对人非小细胞肺癌H460细胞体内抗癌活性及其机制研究

Anti-cancer effect of 1,2:5,6-dianhydrogalactitol on human non-small cell lung cancer H460 and its mechanism

目的:研究二去水卫矛醇(DAG)对人非小细胞肺癌(NSCLC)H460细胞体内抗癌作用及其机制。方法:建立裸鼠人NSCLC H460细胞移植瘤模型,分为模型组、阳性对照组及DAG低、中、高剂量组(DAG-L组、DAG-M组、DAG-H组)。采用TUNEL法检测肿瘤细胞凋亡,分别采用RT-qPCR法和Western blotting法检测肿瘤组织凋亡相关基因和蛋白表达。结果:与模型组比较,DAG各剂量组和阳性对照组瘤体体积和瘤重减小,抑瘤率均高于40%,肿瘤细胞凋亡率增高(均P<0.05);DAG-M组、DAG-H组和阳性对照组Bax、Caspase-3、Caspase-9、P53 mRNA相对表达量升高,DAG-L组Caspase-9 mRNA相对表达量升高,DAG各剂量组Bcl-2 mRNA和蛋白相对表达量均降低,Bax、P53蛋白表达量升高(均P<0.05)。结论:DAG可抑制人NSCLC H460裸鼠皮下移植瘤的生长,其机制与诱导线粒体凋亡途径有关。

Objective:To investigate the anti-cancer effect of 1,2:5,6-dianhydrogalactitol(DAG) on H460 cells of human non-small cell lung cancer and its mechanism.Methods:A model of H460 cell transplant tumor of nonsmall cell lung cancer in nude mice was established,which was divided into model group,positive control group and low,medium and high dose DAG group(DAG-L group,DAG-M group,DAG-H group).The TUNEL assay was used to detect the apoptosis of tumor tissue cells.RT-qPCR and western blotting were used to detect the expression of apoptosis related genes and proteins in tumor tissues.Results:Compared with the model group,the tumor volume and average tumor weight of each DAG dose group and the positive control group were significantly reduced(P<0.05).The tumor inhibition rate was higher than 40%,and the apoptosis rate of tumor cells increased significantly.Compared with the model group,the mRNA expression levels of Bax,caspase-3,caspase-9 and P53 in DAG-M group,DAG-H group and positive control group were significantly increased,the expression of caspase-9 mRNA in DAG-L group was significantly increased,the expression of Bcl-2 mRNA and protein in DAG groups were significantly decreased,and the protein expression of Bax and P53 protein were significantly increased(P<0.05).Conclusion:DAG can inhibit the growth of subcutaneous transplanted tumor of human NSCLC H460 in nude mice,and its mechanism is related to inducing apoptosis pathway of mitochondria.