过表达Mfn2对人乳腺癌裸鼠移植瘤血管表皮生长因子受体的影响

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目的探讨过表达线粒体融合素-2(Mitofusin-2,Mfn2)对表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)表达的影响及对人乳腺癌裸鼠移植瘤生长、血管形成的影响。方法分别构建稳定转染空质粒pEGFP-N1(MCF-7 pEGFP-N1)及转染Mfn2质粒的pEGFP-Mfn2(MCF-7 pEGFP-Mfn2)的MCF-7细胞稳系。分别将人乳腺癌细胞MCF-7、MCF-7 pEGFP-N1、MCF-7 pEGFPMfn2接种于裸鼠右侧乳房垫内,观察裸鼠生长状况,每周两次测量肿瘤大小,绘制肿瘤生长曲线。5周后处死裸鼠,采用免疫组化验证肿瘤Mfn2蛋白的表达并检测CD34来观测肿瘤微血管密度(MVD),检测EGFR蛋白的表达情况。结果 pEGFP-Mfn2组肿瘤明显小于pEGFP-N1组和对照组(P<0.05)。pEGFP-Mfn2组微血管数目明显小于pEGFP-N1组和对照组(P<0.05)。pEGFP-N1组EGFR的表达与对照组相比差异无统计学意义(P>0.05),与对照组、pEGFP-N1组相比pEGFP-Mfn2组EGFR的表达明显降低(P<0.05)。结论 Mfn2明显抑制人乳腺癌裸鼠移植瘤的生长。下调EGFR表达、减少微血管生成可能为其抗肿瘤机制。 Objective To investigate the effect of overexpression of mitofusin-2 (Mfn2) on the expression of epidermal growth factor receptor (EGFR) and its effect on the growth and angiogenesis of human breast cancer xenografts in nude mice. Methods The stable MCF-7 cells were transfected with plasmid pEGFP-N1 (MCF-7 pEGFP-N1) and pEGFP-Mfn2 transfected with Mfn2 plasmid (MCF-7 pEGFP-Mfn2). The breast cancer cells MCF-7, MCF-7 pEGFP-N1 and MCF-7 pEGFPMfn2 were respectively inoculated into the right breast pad of nude mice. The growth of nude mice was observed. The tumor size was measured twice a week and the tumor growth curve was drawn. After 5 weeks, the nude mice were sacrificed. The expression of Mfn2 protein was detected by immunohistochemistry and the expression of MVDs was detected by detecting CD34 expression. Results The tumor size of pEGFP-Mfn2 group was significantly lower than that of pEGFP-N1 group and control group (P <0.05). The number of microvessels in pEGFP-Mfn2 group was significantly lower than that in pEGFP-N1 group and control group (P <0.05). The expression of EGFR in pEGFP-N1 group was not significantly different from that in control group (P> 0.05). The expression of EGFR in pEGFP-N1 group was significantly lower than that in control group and pEGFP-N1 group (P <0.05). Conclusion Mfn2 significantly inhibits the growth of human breast cancer xenografts in nude mice. Decreasing EGFR expression and decreasing angiogenesis may be its anti-tumor mechanism.
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