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

doi:10.13481/j.1671-587x.20200308

吉林大学学报(医学版) ›› 2020, Vol. 46 ›› Issue (03): 476-481.doi: 10.13481/j.1671-587x.20200308

• 基础研究 • 上一篇

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

林久涵¹, 田琳², 张娜娜², 董营¹, 吕航¹, 王丹¹, 曲萌³, 张勇⁴, 孙连坤⁴, 于春艳¹, 刘希⁵

1. 北华大学医学院病理教研室, 吉林吉林 132013;
2. 北华大学医学院临床医学系, 吉林吉林 132013;
3. 北华大学医学院分子生物教研室, 吉林吉林 132013;
4. 吉林大学基础医学院病理生理学系, 吉林长春 130021;
5. 北华大学医学院细胞生物教研室, 吉林吉林 132013

收稿日期:2019-12-04 发布日期:2020-06-11
通讯作者: 于春艳,教授,硕士研究生导师(Tel:0432-64608106,E-mail:gchunyanyu@163.com);刘希,讲师(Tel:0432-64608106,E-mail:liuxijl@163.com) E-mail:gchunyanyu@163.com;liuxijl@163.com
作者简介:林久涵(1994-),男,吉林省吉林市人,在读医学硕士,主要从事肿瘤病理学和病理生理学方面的研究。
基金资助:
国家自然科学基金资助课题（81541148）；吉林省科技厅科研基金资助课题（20180623018TC）；吉林省教育厅科研基金资助课题（JJKH20180356KJ，JJKH20200057KJ）；吉林省卫健委科研基金资助课题（2017J084，2018J092，2019J040）；国家级大学生创新项目资助课题（201810201021）；吉林省大学生创新创业项目资助课题（2018，2019）；北华大学研究生创新计划项目资助课题（2019019）

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

LIN Jiuhan¹, TIAN Lin², ZHANG Nana², DONG Ying¹, LYU Hang¹, WANG Dan¹, QU Meng³, ZHANG Yong⁴, SUN Liankun⁴, YU Chunyan¹, LIU Xi⁵

1. Department of Pathology, College of Medical Sciences, Beihua University, Jilin 132013, China;
2. Department of Clinical Medicine, College of Medical Sciences, Beihua University, Jilin 132013, China;
3. Department of Molecular Biology, School of Medical Sciences, Beihua University, Jilin 132013, China;
4. Department of Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;
5. Department of Cell Biology, College of Medical Sciences, Beihua University, Jilin 132013, China

Received:2019-12-04 Published:2020-06-11

摘要/Abstract

摘要： 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。

关键词: APP/PS1小鼠, 移植黑色素瘤, 线粒体动力学, 线粒体分裂融合, 线粒体自噬

Abstract: 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.

Key words: APP/PS1 mice, transplanted melanoma, mitochondrial dynamics, mitochondial fussion and mission, mitochondrial autophagy

中图分类号:

R739.5

林久涵, 田琳, 张娜娜, 董营, 吕航, 王丹, 曲萌, 张勇, 孙连坤, 于春艳, 刘希. 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[J]. 吉林大学学报(医学版), 2020, 46(03): 476-481.

LIN Jiuhan, TIAN Lin, ZHANG Nana, DONG Ying, LYU Hang, WANG Dan, QU Meng, ZHANG Yong, SUN Liankun, YU Chunyan, LIU Xi. Inhibitory effect of mitochondrial dynamics changes on growth of transplanted melanoma in APP/PS1 mice[J]. Journal of Jilin University(Medicine Edition), 2020, 46(03): 476-481.

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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

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

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