一氧化氮供体JS-K对H22荷瘤小鼠抑瘤作用的研究

Effect of Nitric Oxide Donor(JS-K) on Tumor Growth in H22 Tumor-bearing Mice

目的研究新型一氧化氮供体即O^2-(2,4-二硝基苯基)1-[(4-乙氧羰基)哌嗪-1-yl]偶氮-1-鎓-1,2-二醇(JS-K)对H22荷瘤小鼠肿瘤生长的影响。方法体内建立H22荷瘤小鼠模型,将右腋窝皮下接种H22腹水瘤细胞的Balb/c小鼠随机分为空白对照组、模型组、5-FU 20 mg·kg-1组、JS-K浓度0.75 mg·kg-1和1.50 mg·kg-1组。对照组和模型组尾静脉注射生理盐水,每3天1次;5-FU组腹腔注射5-FU,每天1次;JS-K组分别尾静脉注射不同浓度JS-K,每3天1次。连续14 d,第15天处死小鼠,计算抑瘤率。比色法测定小鼠血清中丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)水平;Western蛋白印迹法检测各组瘤组织中Bcl-2、Bax和cleaved-casapse-3蛋白水平。结果与模型组比较,JS-K药物组平均瘤质量明显小于模型组(均P<0.05);5-FU组、JS-K 0.75 mg·kg-1和1.50 mg·kg-1给药组的抑瘤率分别为60.02%、23.93%和50.26%;JS-K对小鼠ALT和AST无显著影响,可降低肿瘤组织中Bcl-2蛋白表达,升高Bax和cleaved-casapse-3蛋白表达。结论 JS-K对H22荷瘤小鼠的抑瘤作用与其诱导肿瘤细胞凋亡有关。

ObjectiveTo investigate the regulation effects of nitric oxide donor,{O2(2,4dinitrophenyl)1[(4ethoxycarbonyl)piperazin1yl]diazen1ium1,2diolate}(JS K),on proliferation in H22tumor bearing mice.MethodsThe experimental animal model of H22tumor bearing mice was established by H22ascitic tumor cell subcutaneous inoculation in right axillary fossa of Balb/c mice.The inoculated Balb/c mice were randomly divided into five groups.The control and model group received0.9%normal saline via tail intravenous once every3days.The positive control group was treated with fluorouracil(5FU)at a dosage of20mg·kg-1by intraperitoneal injection once a day.The JS K groups received tail intravenous injection at different dosages(0.75mg·kg-1and1.5mg·kg-1)once every3days.All groups were treated for14days.At the end of the study,all the mice were sacrificed,and the tumor of the mice were isolated and weighed immediately to calculate the tumor growth inhibition rate.The levels of serum alanine transaminase(ALT)and aspartate transaminase(AST)were determined by colorimetric method.The expressions of apoptotic related proteins such as Bcl2,Bax and cleaved caspase3were observed by Western blot assay.