Regulation of nitric oxide donor JS-K on tumor energy metabolism in H22 tumor-bearing mice

Ling LIU,Zi-le HUANG,Jian-gang WANG

(Department of Pharmacy,Medical College,Henan University of Science and Technology,Luoyang 471003,China)

T1-20

Regulation of nitric oxide donor JS-K on tumor energy metabolism in H22 tumor-bearing mice

Ling LIU,Zi-le HUANG,Jian-gang WANG

(Department of Pharmacy,Medical College,Henan University of Science and Technology,Luoyang 471003,China)

OBJECTIVETo investigate the regulation of{O2(2,4-dinitrophenyl)1-〔(4-ethoxycarbonyl)piperazin-1-yl〕diazen-1-ium-1,2-diolate}(JS-K),anitric oxide donor,on tumor energy metabolism in H22 tumor-bearing mice.METHODSThe hepatoma animal model in BALB/c mice was established with H22 cell line.The JS-K group and model group were

JS-K(0.75 and 1.5 mg·kg-1)and saline via tail intravenous once every 3 d for 14 d,received 5 injections,respectively.The positive group was received 5-FU 20 mg·kg-1by intraperitoneal injection once a day for 14 d.On the 15thday mice were sacrificed.The tumor growth inhibition rate were calculated.The activities of hexokinase(HK),phospho⁃fructo kinase(PFK),pyruvate kinase(PK),succinate dehydrogenase(SDH),adenosine triphosphatase(ATPase),and the levels of lactic acid(LD)and adenosine triphosphate(ATP)in tumor tissues were de⁃termined by colorimetric method.RESULTSCompared with model group,the tumor mass of JS-K 0.75 and 1.5 mg·kg-1group was significantly reduced(P＜0.01)，and the tumor growth inhibition rate was 23.9%and 50.3%,respectively.The activity of HK,PFK,PK,SDH and ATPase of tumor tissue in model group was(22.6±3.7,14.4±2.6,12.9±3.2 and 10.5±2.6)U·g-1protein and(0.70±0.10)μmolPi·mg-1protein per hour,respectively;which in JS-K 1.5 mg·kg-1group was dropped by 42.0%,26.6%,22.7%,23.3%and 21.7%(P＜0.01,P＜0.05).Compared with the model group,the level of ATP and LD in JS-K group was dropped(P＜0.01).CONCLUSIONJS-K can inhibit the growth of tumor in H22 tumor-bearing mice and its mechanism may be related to regulating the tumor energy metabolism with inhibition of glycolysis and aerobic oxidation.

nitric oxide donor;diazeniumdiolate;Warburg effect

The project supported by National Natural Science Foundation of China(81502627);and the Young Backbone Teachers Assistance Scheme of Henan Province Colleges and Universities(2016GGJS-065)

Ling LIU,E-mail:liuling921@126.com,Tel:(0379)64830345