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[目的]研究一氧化氮(NO)供体硝酸异山梨酯(ISDN)对肿瘤生长的影响。[方法]①体内实验:以HepA肿瘤细胞接种小鼠左侧足垫制作荷瘤动物模型。小鼠连续腹腔注射ISDN,200μg/只,以生理盐水代替药物作为对照。给药后7d、14d观察尿液NO2-+NO3-含量、肿瘤大小。②体外实验:将HepA肿瘤细胞培养于含2μg/ml、10μg/ml、100μg/mlISDN的培养液中48h,用MTT法测定肿瘤细胞增殖程度。[结果]①ISDN组小鼠尿液NO2-+NO3-含量明显高于对照组(P<0.01);而ISDN组小鼠肿瘤体积明显小于对照组(P<0.05和P<0.01)。②3种浓度的ISDN可降低培养HepA肿瘤细胞增殖,在10μg/ml、100μg/ml浓度时,与对照组比较具有显著差异(P<0.01),且以100μg/ml浓度组抑制作用最强。[结论]NO供体ISDN可抑制肿瘤的生长,NO对肿瘤细胞增殖的直接抑制作用可能是其抗肿瘤作用机理的一部分。
[Objective] To investigate the effect of isonosine mononitrate (ISDN) on tumor growth of nitric oxide (NO) donor. [Method] In vivo experiment: The tumor-bearing animal model was made by inoculating the left foot pad of HepA tumor cells in mice. Mice were injected intraperitoneally with ISDN, 200μg / mouse, with saline instead of drug as a control. After 7d and 14d, the urinary NO2- + NO3- and tumor size were observed. ② In vitro experiments: HepA tumor cells were cultured in culture medium containing 2μg / ml, 10μg / ml and 100μg / mlISDN for 48h. The degree of tumor cell proliferation was determined by MTT assay. [Results] ① The content of NO2- + NO3- in the urine of the ISDN group was significantly higher than that of the control group (P <0.01), while the tumor volume of the ISDN group was significantly smaller than that of the control group (P <0.05 and P <0.01). (3) ISDN at 3 concentrations reduced the proliferation of HepA cells, and had significant difference (P <0.01) at 10μg / ml and 100μg / ml compared with the control group, and showed the strongest inhibitory effect at 100μg / ml. [Conclusion] NO donor ISDN can inhibit tumor growth. The direct inhibition effect of NO on tumor cell proliferation may be part of the anti-tumor mechanism.