三氧化二砷联合TNP-470对裸鼠人肝癌移植瘤的影响

Effect and mechanism of arsenic trioxide combined with TNP-470 on nude mice breaking human hepatocellular carcinoma

目的:探讨三氧化二砷(As2O3)联合烟曲霉的提取物烟曲霉醇(TNP-470)对裸鼠人肝癌移植瘤生长的影响及其作用机制。方法:人肝癌转移模型(HCC)-LCI-D20原位移植瘤裸鼠32只,随机分4组(每组8只)给药:As2O3联合TNP-470组、As2O3组、TNP-470组、生理盐水(NS)对照组,给药21天后,对裸鼠移植瘤大小、肿瘤微血管密度(MVD)、免疫组化、透射电镜结果进行观察。结果:As2O3组、TNP-470组及联合组的平均瘤重及平均瘤体积均低于对照组(P<0.05);计算两药相互作用系数(CDI)值:瘤重CDI(0.95)<1,体积CDI(0.89)<1,两药有协同抑制移植瘤生长的作用。As2O3组抑制移植瘤VEGF、EGFR的表达;TNP-470组抑制移植瘤EGFR的表达,对移植瘤VEGF的表达无影响;联合组明显抑制移植瘤EGFR的表达,抑制移植瘤VEGF的表达作用等同As2O3组。裸鼠原位移植瘤的光镜、电镜下观察结果有意义;各用药组裸鼠原位移植瘤的MVD值均低于对照组(P<0.05)。结论:As2O3联合TNP-470协同抑制裸鼠人肝癌移植瘤的血管新生,能有效抑制移植瘤生长。

Objective：To study the growing effects as well as mechanism of action for a high metastatic model of nude mice breaking human hepatocellular carcinoma in Arsenic Trioxide（As203） combined with Aspergillus fumigatus extractive（TNP- 470）. Methods： To observe the following index： metastatic neoplasmas, microvessel density （ MVD）, immunohistochemistry and electron microscope, 32 （HCC） - LCI - D20 nude mise were divided into four groups （ 8 per group） ： As2 03 combining TNP - 470, As2 03 , TNP - 470, NS control group randomly administered medicine for 21 days. Results： To compare NS control group, there was a significant difference （P 〈 0.05 ）in average weight and volume of metastatic neoplasmas among groups of As2 03 and TNP - 470 ; there were CDI （ 0.95 ） 〈 1 of tumor weights and CDI （0.89） 〈 1 of tumor volumes by computing the interactive coefficient of two drugs, which had the synergistic action. The expression of VEGF and EGFR in transplantation tumor was inhibited in As2 03 group , but only EGFR was inhibited in TNP -470 group;the depressant effect of As2 03 combined with TNP -470 group in the expression of EGFR of transplantation tumor was more well, but of VEGF equals the depressant effect of As2 03 group;there was difference in the metastatic neoplasmas of nude mice by light microscope and electron microscope; MVD of the drug groups was lower than MVD of the NS control group （ P 〈 0.05 ）. Conclusion： There is a positive cooperation for As203 combined with TNP- 470 against human hepatocellular carcinoma as well as angiogenesis.