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目的 探讨卵巢上皮性癌组织中缺氧诱导因子 (HIF) 1α与血管内皮生长因子 (VEGF)及微血管密度 (MVD)的相关性。方法 用卵巢癌细胞株SKOV3种植于裸鼠背部皮下形成移植瘤。对移植瘤组织给予生理盐水 2 0 0 μl为对照组 ;给予HIF 1α抑制剂 (西罗莫司 ) 4mg/kg ,为西罗莫司组 ;给予VEGF抑制剂 (舒林酸 ) 10 0mg ,为舒林酸组。用免疫组化及RT PCR的方法 ,检测 3组肿瘤组织中HIF 1α、VEGF的表达以及MVD。结果 对照组HIF 1α及VEGF蛋白的表达为中、强阳性 ;西罗莫司组HIF 1α和VEGFmRNA表达均显著下降 ,为无表达或弱表达 ,两组比较 ,差异有显著性(P <0 0 5 )。经统计学检验 ,对照组与西罗莫司组HIF 1α和VEGFmRNA表达密切相关 (相关系数为 0 82 6 4 ,P <0 0 1) ;对照组HIF 1α靶基因 (肿瘤组织葡萄糖转运蛋白 1)的mRNA值为 0 8333,MVD为 31± 8,西罗莫司组HIF 1α肿瘤组织葡萄糖转运蛋白 1的mRNA值为 0 4 6 6 7,MVD为 13±5 ,两组具有相关性 (相关系数为 0 4 84 2 ,P <0 0 5 )。舒林酸组HIF 1α蛋白表达无改变 ,MVD表达为2 2± 6。结论 当HIF 1α的表达受到抑制时 ,VEGF的表达随之下降 ;HIF 1α对VEGF蛋白及mRNA的表达具有调节作用 ,从而使MVD降低。
Objective To investigate the relationship between hypoxia inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) and microvessel density (MVD) in epithelial ovarian cancer. Methods The ovarian cancer cell line SKOV3 was implanted subcutaneously in nude mice to form xenografts. The transplantation tumor tissue was given with 200 μl of saline as the control group; 4 mg / kg of HIF 1α inhibitor (sirolimus) was administered to the sirolimus group; and 10 0 mg of VEGF inhibitor (sulindac) was given as Sulindac group. Immunohistochemistry and RT PCR were used to detect the expression of HIF-1α, VEGF and MVD in the three tumor tissues. Results The expression of HIF-1α and VEGF protein in the control group was moderately and strongly positive. The expressions of HIF-1α and VEGF mRNA in sirolimus group were significantly decreased, with no or weak expression, the difference was significant (P <0 0 5). Statistically, the expression of HIF-1αand VEGFmRNA in the control group and sirolimus group were closely related (the correlation coefficient was 0 82 6 4, P 0 01); in the control group HIF 1α target gene (tumor tissue glucose transporter 1) MRNA was 0 8333, MVD was 31 ± 8, mRNA expression of glucose transporter 1 in HIF 1α tumor tissue of sirolimus group was 0 466 7, MVD was 13 ± 5, the two groups had correlation (correlation coefficient Is 0 4 84 2, P <0 0 5). There was no change in HIF-1α protein expression in sulindac group, with an MVD of 22 ± 6. Conclusions When the expression of HIF-1α is inhibited, the expression of VEGF is decreased. HIF-1α has a regulatory effect on the expression of VEGF protein and mRNA, which leads to the decrease of MVD.