丹参联合5-Fu对小鼠Lewis肺癌中HIF-1α、VEGF和MVD表达的影响

Effects of the expression of HIF- 1α,VEGF and MVD of Lewis lung carcinoma in mice of Danshen united 5- Fu

目的通过检测丹参联合5-Fu对小鼠Lewis肺癌低氧诱导因子-lα(HIF-lα)、血管内皮生长因子(VEGF)浓度和微血管密度(MVD),分析丹参对实体肿瘤局部血供和乏氧细胞氧压的影响,探讨丹参配合5-Fu提高疗效的机理。方法建立Lewis肺癌荷瘤鼠模型后,将60只小鼠随机均分为模型组、丹参低剂量组(丹低组)、丹参高剂量组(丹高组)、5-Fu组、丹参低剂量+5-Fu组(丹低+5-Fu组)、丹参高剂量+5-Fu组(丹高+5-Fu组)。于接种第2天起每天ip给药各组大鼠,末次给药24 h后检测肿瘤细胞中HIF-lαmRNA表达值、血清VEGF浓度和MVD。结果 5-Fu组、丹高+5-Fu组较模型组中HIF-lαmRNA的表达值降低(P<0.01),丹高+5-Fu组较5-Fu组有降低HIF-lαmRNA的表达值的趋势;丹高组、5-Fu组、丹低+5-Fu组及丹高+5-Fu组血VEGF浓度较模型组的降低(P<0.05),丹低+5-Fu组较5-Fu组降低趋势更为明显;丹高组、5-Fu组、丹低+5-Fu组及丹高+5-Fu组瘤组织中MVD较模型组的均降低(P<0.05),丹低+5-Fu组与5-Fu组相比,降低MVD的趋势更为明显。结论丹参联合5-Fu能降低HIF-1αmRNA表达值及血VEGF浓度,说明丹参可增加乏氧细胞氧压、抑制肿瘤微血管的生成,从而增强5-Fu的化疗效果。

OBJECTIVE To measure the effect of the expression of HIF -1α, VEGF and MVD of Lewis Lung Carcinoma in mice with Danshen ＋ 5 - Fu and investigate the supplement of blood and oxygen pressure of hypoxia ceils in the solid tumor, and analyses the mechanism of improve effect to tumor with Danshen ＋ 5 - Fu. METHODS 60 Lewis lung tumor mice were randomly divided into normal control group, Danshen low - dose group, Danshen high - dose group, 5 - Fu group, Danshen low - dose and 5 - Fu group, Danshen high - dose and 5 - Fu group. Each group was inoculated by intraperitoneal injection since the second day. Then all mice were obtained orbital blood after 24 h of the last administration, the expression of HIF -1α mRNA in tumor cells, the vascular endothelial growth factor expression levels and MVD were determined. RESULTS Compared with model group, the expression of HIF-1α mRNA value of 5 - Fu and Danshen high - dose group decreased （P 〈 0.01 ）. Compared to 5 - Fu group, Danshen high - dose and 5 - Fu group significantly reduced the expression of HIF -1α mRNA value trend. Compared with model group, the concentration of VEGF in serum, tumor microvessel density index of the other groups reduced（ P 〈 O. 05 ） between two groups of 5 - Fu, but compared to 5 - Fu group, Danshen low - dose and 5 - Fu group significantly reduced the tow trends. CONCLUSION Danshen ＋ 5 - Fu may reduce HIF -1α mRNA expression, the concentration of VEGF and MVD in serum to increase oxygen pressure of hypoxia cells increased, inhibit tumor angiogenesis, thus enhancing chemotherapy effect on mice.