线粒体动力学改变对APP/PS1小鼠移植黑色素瘤生长的抑制作用

目的：探讨线粒体动力学的变化对APP/PS1转基因小鼠移植黑色素瘤生长的抑制作用及其机制。方法：将C57BL/6J （C57）和APP/PS1雄性小鼠分为C57移植瘤组（n=7）和APP/PS1移植瘤组（n=7）。观察2组小鼠肿瘤出现时间并计算肿瘤体积，绘制移植瘤生长曲线。光学显微镜观察2组小鼠肿瘤组织形态表现，Western blotting法检测2组小鼠肿瘤组织中线粒体融合蛋白2（Mfn2）、动力相关蛋白1（Drp1）、线粒体分裂蛋白1（Fis1）、泛素化及多泛素化蛋白、LC3、PINK1及Parkin蛋白表达水平。结果：C57移植瘤组和APP/PS1移植瘤组小鼠皮肤下均见肿瘤组织，肿瘤细胞内呈现黑色素颗粒。与C57移植瘤组比较，APP/PS1移植瘤组小鼠出瘤时间晚，肿瘤组织体积小（P<0.05）。小鼠肿瘤组织中Mfn2表达水平降低（P<0.05），Fis1和Drp1表达水平升高（P<0.05），泛素化及多聚泛素化蛋白、LC3-Ⅱ、PINK1和Parkin蛋白表达水平升高（P<0.05）。结论：APP/PS1小鼠移植瘤模型肿瘤生长缓慢，其机制可能与PINK1/Parkin通路参与线粒体自噬有关。

Inhibitory effect of mitochondrial dynamics changes on growth of transplanted melanoma in APP/PS1 mice

Objective: To investigate the inhibitory effect of mitochondrial dynamics changes on the tumor growth of transplanted melanoma in the APP/PS1 the mice and its mechanism. Methods: The male C57BL/6J(C57) and APP/PS1 mice were divided into C57 transplantation tumor group (n=7) and APP/PS1 transplantation tumor group(n=7). The tumor appearance time was observed and the tumor volume of the mice in two groups were calculated and the growth curves of the mice in two groups were drawn. The morphology of tumor tissue of the mice in two groups was observed under light microscope,the expression levels of mitofusion 2(Mfn2), dynamin related protein (Drp1), fission 1(Fis1), ubiquitin and polyubiquitin, LC3-Ⅱ, PTEN induced putative kinase 1(PINK1) and Parkin proteins in tumor tissue of the mice in two groups were detected by Western blotting method. Results: The tumor tissue under the skin of the mice in C57 transplantation tumor group and APP/PS1 transplantation tumor group was found with the melanoma granules in the tumor cells. Compared with C57 transplantation tumor group, the tumor appearance time of the mice in APP/PS1 transplantation tumor group was late, and the tumor volume was decreased (P<0.05); the expression level of Mfn2 protein in tumor tissue of the mice was decreased(P<0.05); the expression levels of Drp1 and Fis1 proteins were increased (P<0.05), and the expression levels of ubiquitin and polyubiqitin, LC3-Ⅱ, PINK1 and Parkin proteins in tumor tissue of the mice in APP/PS1 transplantation tumor group were all increased(P<0.05). Conclusion: The growth of tumor in the APP/PS1 mice with transplanted melanoma is slow,and its mechanism may be related to PINK1/Parkin pathway involved in the mitochondrial autophagy.