一氧化氮供体JS-K对H22荷瘤小鼠肿瘤能量代谢的调节作用
发布时间：2018-11-06 10:22
【摘要】：目的研究新型一氧化氮(NO)供体O~2-(2,4-二硝基苯基)1-[(4-乙氧羰基)哌嗪-1-yl]偶氮-1-摀-1,2-二醇(JS-K)对H22荷瘤小鼠肿瘤能量代谢的调节作用。方法 BALB/c小鼠皮下接种H22细胞建立荷瘤小鼠模型,并随机分为模型组、氟尿嘧啶(5-FU)组、JS-K 0.75和1.50 mg·kg~(-1)组。JS-K组和模型组小鼠每3 d尾静脉注射不同剂量JS-K或生理盐水,连续14 d(共给药5次);5-FU组每天1次ip给予5-FU 20 mg·kg~(-1),给药后第15天将小鼠处死,分离胸腺、脾和完整瘤体,并称取其质量,计算抑瘤率和脏器系数、比色法检测瘤组织中已糖激酶(HK)、丙酮酸激酶(PK)、磷酸果糖激酶(PFK)、琥珀酸脱氢酶(SDH)和腺苷三磷酸酶(ATPase)活性,以及乳酸和ATP水平;Western蛋白印迹法检测各组瘤组织中缺氧诱导因子-1α(HIF-1α)和己糖激酶Ⅱ(HKⅡ)蛋白表达。结果与模型组比较,JS-K0.75和1.50mg·kg~(-1)组瘤质量显著下降(P0.01),抑瘤率分别为23.9%和50.3%JS-K 0.75和1.50 mg·kg~(-1)组小鼠胸腺系数和脾系数与模型组无明显差异比色法检测结果显示,JS-K 1.50 mg·kg~(-1)组瘤组织中HK,PFK,SDH,PK和ATPase活性较模型组的[22.6±3.7,14.4±2.6,(10.5±2.6)U·g~(-1)蛋白,(12.9±3.2)kU·g~(-1)蛋白和(0.70±0.10)mmolPi·g~(-1)蛋白·h~(-1)]分别下降了42.0%,26.6%,23.3%,22.7%和21.7%(P0.01,P0.05);JS-K 1.50 mg·kg~(-1)组瘤组织中ATP水平较模型组下降16.6%(P0.01);JS-K0.75和1.50mg·kg~(-1)组瘤组织中乳酸水平较模型组分别下降38.7%和59.4%(P0.01)。Western蛋白印迹检测结果显示,与模型组比较,JS-K 1.50 mg·kg~(-1)组瘤组织中HIF-1α(蛋白表达显著降低(P0.01);JS-K 0.75和1.50 mg·kg~(-1)组HKⅡ蛋白表达均显著降低(P0.05,P0.01)。结论 JS-K能抑制H22荷瘤小鼠肿瘤生长,其机制可能与抑制糖酵解和有氧氧化途径从而调节肿瘤能量代谢有关。
[Abstract]:Objective to study the effect of a new nitric oxide (NO) donor, Of2- (2H2-dinitrophenyl) 1- [(4-ethoxycarbonyl) piperazine-1-yl] azo-1-fu-1- 2-diol (JS-K) on tumor energy of H22 tumor-bearing mice. The regulation of metabolism. Methods BALB/c mice were inoculated subcutaneously with H22 cells to establish tumor-bearing mice model, and were randomly divided into model group, fluorouracil (5-FU) group. JS-K 0.75 and 1.50 mg kg~ (-1) groups. Mice in JS-K group and model group were injected with different doses of JS-K or normal saline every 3 days for 14 days (5 times). 5-FU group was given 5-FU 20 mg kg~ (-1) once a day. The mice were killed on the 15th day, thymus, spleen and complete tumor were separated, and the tumor inhibition rate and organ coefficient were calculated. The activities of hexokinase (HK), pyruvate kinase (competitive), phosphofructokinase (PFK), succinate dehydrogenase (SDH) and adenosine triphosphatase (ATPase), as well as the levels of lactic acid and ATP were detected by colorimetric method. The expression of hypoxia inducible factor-1 伪 (HIF-1 伪) and hexokinase 鈪，
本文编号：2314001
[Abstract]:Objective to study the effect of a new nitric oxide (NO) donor, Of2- (2H2-dinitrophenyl) 1- [(4-ethoxycarbonyl) piperazine-1-yl] azo-1-fu-1- 2-diol (JS-K) on tumor energy of H22 tumor-bearing mice. The regulation of metabolism. Methods BALB/c mice were inoculated subcutaneously with H22 cells to establish tumor-bearing mice model, and were randomly divided into model group, fluorouracil (5-FU) group. JS-K 0.75 and 1.50 mg kg~ (-1) groups. Mice in JS-K group and model group were injected with different doses of JS-K or normal saline every 3 days for 14 days (5 times). 5-FU group was given 5-FU 20 mg kg~ (-1) once a day. The mice were killed on the 15th day, thymus, spleen and complete tumor were separated, and the tumor inhibition rate and organ coefficient were calculated. The activities of hexokinase (HK), pyruvate kinase (competitive), phosphofructokinase (PFK), succinate dehydrogenase (SDH) and adenosine triphosphatase (ATPase), as well as the levels of lactic acid and ATP were detected by colorimetric method. The expression of hypoxia inducible factor-1 伪 (HIF-1 伪) and hexokinase 鈪，
本文编号：2314001
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