清燥救肺汤对荷Lewis小鼠肺癌细胞增殖相关糖酵解乳酸生成的影响

Effect of Qingzao Jiufei Tang on Lung Cancer Cells Proliferation Related Production of Glycolysis Lactic Acid in Lewis Mice

目的：观察清燥救肺汤对荷Lweis小鼠肺癌细胞增殖相关糖酵解乳酸生成的影响,探讨其作用机制。方法：50只雄性C57BL/6J小鼠,随机分为模型组,化疗组,清燥救肺汤高、中、低剂量组,每组10只。右腋下注射Lewis肺癌细胞建立肺癌荷瘤模型,清燥救肺汤高、中、低剂量组以11,5.5,2.75 g·kg（-1）·d（-1）造模前2周灌胃给药,化疗组以50 mg·kg（-1）·（2d）（-1）腹腔注射给药,模型组以等体积生理盐水灌胃给药,接种后继续给药2周后处死各组小鼠并取瘤称重,蛋白免疫印迹法（Western blot）检测低氧诱导因子-α亚基（hypoxia inducible factor,HIF-）α）,原癌基因蛋白（cancer-myc,C-myc）表达,酶联免疫吸附测定法（ELISA）检测乳酸水平以及乳酸脱氢酶-A（lactate dehydrogenase-A,LDH-A）活性。结果：与模型组比较,清燥救肺汤高、中、低剂量组及化疗组瘤质量,乳酸含量显著降低（P〈0.01）;清燥救肺汤高、中、低剂量组及化疗组中肺癌细胞C-myc蛋白表达,LDH-A活性明显降低（P〈0.05,P〈0.01）;清燥救肺汤高、中剂量组及化疗组HIF-1α蛋白表达显著降低（P〈0.01）。结论：清燥救肺汤可通过抑制HIF-1α蛋白表达,导致C-myc蛋白表达下调,从而降低LDH-A活性,减少肺癌细胞糖酵解乳酸的生成,从而达到抑制荷Lewis小鼠肺癌细胞增殖的功效。

Objective： To discuss the effect of Qingzao Jiufei Tang on the lung cancer cells proliferation related production of glycolysis lactic acid in Lewis-bearing mice,and investigate its possible mechanism. Method：50 male C57 BL/6 J mice were randomly divided into model group,chemotherapy group,high,medium and low dose Qingzao Jiufei Tang groups,n = 10 in each group. Animal models were induced with the right subaxillary injection of Lewis cells,and Qingzao Jiufei Tang groups started medication two weeks before modeling（11,5. 5,and 2. 75 g · kg（-1）· d（-1））; in chemotherapy group, drug was given by intraperitoneal injection at50 mg·kg（-1）·（2 d）（-1）; same volume of saline was given by intragastric administration after two weeks of drug administratio. After 14 d modeling,the mice were killed and tumors were weighed. The protein expression levels of hypoxia inducible factor（HIF）-1α and cancer-myc（C-myc） were detected by Western blot method,and lactate dehydrogenase-A（LDH-A） activity was detected by enzyme linked immunosorbent assay（ELISA）. Result： As compared with model group,the tumor weight,lactic acid content were significantly reduced（P 〈 0. 01）,and the protein expression of C-myc in lung cancer cells and LDH-A activity were reduced（P 〈 0. 05,P 〈 0. 01） in Qingzao Jiufei Tang high dose group,medium dose group,low dose group and chemotherapy group（P 〈 0. 01）;the protein expression of HIF-1α was significantly reduced in Qinzao Jiufei Tang high and medium dose groups and chemotherapy group（P 〈 0. 01）. Conclusion： Qingzao Jiufei Tang can inhibit the proliferation of Lewis mice lung cancer cells by inhibiting the expression of HIF-α protein,down-regulating C-myc protein,reducing the activity of LDH-A and reducing the production of lactic acid in lung cancer cells.