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背景与目的:YH-16是新合成的重组人血管内皮抑制素,Ⅱ期临床试验已证实YH-16联合化疗治疗晚期非小细胞肺癌具有协同作用。本文探讨血管生成抑制剂YH-16对结肠癌肝转移的抑制作用。方法:MTT法测定血管生成抑制剂YH-16对血管内皮细胞和结肠癌CT26细胞的IC50;经小鼠脾脏下极包膜下注入CT26细胞建立结肠癌肝转移模型,60只小鼠随机分为对照组、低剂量YH-16组、中剂量YH-16组、高剂量YH-16组,YH-16剂量分别为0mg/kg、0.40mg/kg、0.75mg/kg和1.50mg/kg,术后2周观察各组小鼠肝转移情况,采用免疫组化方法检测肝转移瘤组织中血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达和肿瘤微血管密度(microvesseldensity,MVD)。结果:(1)YH-16对结肠癌CT26细胞和血管内皮细胞的IC50分别为(2.16±0.28)μg/ml和(0.64±0.10)μg/ml,前者是后者的3.38倍;(2)对照组,低、中、高剂量YH-16组肝转移率分别为100.0%、92.3%、80.0%和73.3%。高剂量YH-16组肝转移瘤数目明显低于对照组、低剂量YH-16组和中剂量YH-16组(P值均<0.05);(3)对照组,低、中、高剂量YH-16组脾脏肿瘤体积的中位数分别为1.180cm3、1.201cm3、0.887cm3和0.781cm3,四组比较无显著性差异(P>0.05);(4)YH-16各剂量组肝转移瘤组织中VEGF的表达较对照组无明显降低,四组肝转移瘤的MVD分别为65.00±9.58、58.15±8.81、51.60±7.10和44.53±11.47,中、高剂量YH-16组的MVD计数较对照组明显降低,高剂量YH-16组MVD计数较中剂量和低剂量YH-16组明显降低(P值均<0.05)。结论:血管生成抑制剂YH-16可以明显抑制结肠癌肝转移。
BACKGROUND & OBJECTIVE: YH-16 is a newly synthesized recombinant human endostatin. Phase II clinical trial has proved that YH-16 combined with chemotherapy has a synergistic effect on advanced non-small cell lung cancer. This article discusses the inhibition of angiogenesis inhibitor YH-16 on liver metastasis of colon cancer. Methods: The IC50 of vascular endothelial cell inhibitor YH-16 and CT26 cells in colon carcinoma was determined by MTT assay. CT26 cells were injected subcutaneously into mouse spleen to establish a model of liver metastasis of colon cancer. Sixty mice were randomly divided into In the control group, the doses of YH-16, YH-16, YH-16 and YH-16 were 0mg / kg, 0.40mg / kg, 0.75mg / kg and 1.50mg / kg respectively The liver metastasis of mice in each group was observed 2 weeks later. The expression of vascular endothelial growth factor (VEGF) and the microvessel density (MVD) in liver metastases were detected by immunohistochemistry. Results: (1) The IC50 of YH-16 on colon cancer CT26 cells and vascular endothelial cells were (2.16 ± 0.28) μg / ml and (0.64 ± 0.10) μg / ml respectively, In the control group, the liver metastasis rates of low, medium and high dose YH-16 group were 100.0%, 92.3%, 80.0% and 73.3% respectively. The number of hepatic metastases in high dose YH-16 group was significantly lower than that in control group, low dose YH-16 group and middle dose YH-16 group (all P <0.05); (3) The control group, low, middle and high dose YH (P> 0.05). (4) The median of tumor volume of -16 group was 1.180cm3,1.201cm3,0.887cm3 and 0.781cm3 respectively, there was no significant difference between the four groups (P> 0.05). (4) The MVD of the four groups of liver metastases were 65.00 ± 9.58,58.15 ± 8.81,51.60 ± 7.10 and 44.53 ± 11.47, respectively. Compared with the control group, the MVD of medium and high doses of YH-16 group was significantly lower than that of the control group (P <0.05). The MVD in high dose YH-16 group was significantly lower than that in middle dose and low dose YH-16 group (all P <0.05). Conclusion: The angiogenesis inhibitor YH-16 can significantly inhibit liver metastasis of colon cancer.