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目的:探讨双氢青蒿素(DHA)联合吉西他滨(GEM)对裸鼠胆管癌细胞株(QBC939)皮下移植瘤生长的抑制作用及可能机制。方法:建立人胆管癌裸鼠皮下移植瘤模型,模型建立后28只裸鼠随机分成4组,对照组、DHA组、GEM组、DHA+GEM联合干预组,每组7只。检测各组裸鼠皮下移植瘤体积的变化,21 d后处死裸鼠,检测各组转移瘤重量并计算抑瘤率,免疫组化法检测瘤组织血管内皮生成因子(VEGF)表达水平,CD31标记血管内皮细胞测定肿瘤的微血管密度(MVD)。结果:DHA组、GEM组、联合用药组的移植瘤体积和重量小于对照组,联合用药组的移植瘤体积和重量明显小于单独用药组;DHA组的VEGF、MVD表达与对照组比较,差异无统计学意义(P>0.05);GEM组的VEGF表达较对照组减少但与DHA组无差异,GEM组的MVD表达较对照与DHA组均减少;联合用药组VEGF、MVD表达较对照组、单药组均减少。结论:DHA对肿瘤生长有一定的抑制作用,而GEM具有更明显的抗肿瘤作用,两者联合应用可达到较好的协同作用,抑瘤作用更加明显,DHA有可能对GEM化疗有增敏作用。抑制肿瘤机制可能与抑制肿瘤组织血管生成等有关。
Objective: To investigate the inhibitory effect of dihydroartemisinin (DHA) combined with gemcitabine (GEM) on the growth of subcutaneous xenograft in nude mice with cholangiocarcinoma cell line QBC939 and its possible mechanism. Methods: A subcutaneous xenograft model of human cholangiocarcinoma was established. Twenty-eight nude mice were randomly divided into 4 groups: control group, DHA group, GEM group and DHA + GEM intervention group, with 7 mice in each group. The tumor volume of subcutaneous xenografts in nude mice in each group was detected. After 21 days, the nude mice were sacrificed, the weight of metastatic tumor in each group was measured and the tumor inhibition rate was calculated. The expression of vascular endothelial growth factor (VEGF) Vascular endothelial cells were assayed for microvessel density (MVD) of the tumor. Results: The volume and weight of transplanted tumor in DHA group, GEM group and combination group were smaller than those in control group. The volume and weight of transplanted tumor in combination group were significantly smaller than that in single drug group. The expression of VEGF and MVD in DHA group was significantly lower than that in control group (P> 0.05). The VEGF expression in GEM group was lower than that in control group but not in DHA group. The MVD expression in GEM group was lower than that in control group and DHA group. The expression of VEGF and MVD in GEM group was significantly higher than that in control group The medicine group reduced. Conclusion: DHA has a certain inhibitory effect on tumor growth, while GEM has a more obvious anti-tumor effect. The combination of the two can achieve better synergistic effect, and the anti-tumor effect is more obvious. DHA may sensitize GEM chemotherapy . Inhibition of tumor mechanisms may be related to inhibition of tumor angiogenesis and so on.