人类脐带间充质干细胞抑制肝内胆管癌细胞生长的机制

doi:10.6040/j.issn.1671-7554.0.2013.684

山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (8): 1-5.doi: 10.6040/j.issn.1671-7554.0.2013.684

• 基础医学 • 下一篇

人类脐带间充质干细胞抑制肝内胆管癌细胞生长的机制

刘娟, 韩国庆, 刘慧, 秦成勇

山东大学附属省立医院消化内科, 山东济南 250021

收稿日期:2013-11-14 修回日期:2014-07-02 出版日期:2014-08-10 发布日期:2014-08-10
通讯作者: 秦成勇。E-mail：qchengyong@aliyun.com E-mail:qchengyong@aliyun.com
基金资助:
国家自然科学基金（81250040）；山东省自然科学基金（ZR2010HM046）；中国博士后科学基金（2013M541926）；山东省博士后创新专项资助项目（201302031）

Mechanism of human umbilical cord mesenchymal stem cells suppressing cholangiocarcinoma cell growth

LIU Juan, HAN Guoqing, LIU Hui, QIN Chengyong

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China

Received:2013-11-14 Revised:2014-07-02 Online:2014-08-10 Published:2014-08-10

摘要/Abstract

摘要： 目的探讨人类脐带间充质干细胞（hUC-MSCs）对肝内胆管癌细胞生长的影响，深入了解其分子机制。方法采用hUC-MSCs条件培养基作用于肝内胆管癌HCCC-9810细胞，通过Transwell 共培养实验、MTT比色实验、DNA断裂实验等方法检测细胞增殖和细胞凋亡，通过Western blotting及免疫荧光染色方法检测相关凋亡通路中蛋白质表达水平。结果细胞增殖实验证实，间充质干细胞条件培养基对HCCC-9810细胞的增殖抑制表现出时间和剂量依赖性，且抑制作用是通过诱导细胞凋亡介导，增殖抑制率由12.87%升至50.98%，凋亡率由10.1%升至49.67%。免疫印迹实验结果显示，p-AKT、p-GSK-3β表达被下调。结论人类脐带间充质干细胞条件培养基可抑制肝内胆管癌细胞的生长，其分子机制与抑制PI3K/Akt信号通路有关。

关键词: 脐带间充质干细胞, 肝内胆管癌, Akt通路

Abstract: Objective To explore the effect of human umbilical cord mesenchymal stem cells on cholangiocarcinoma HCCC-9810 cells and its molecular mechanism. Methods HCCC-9810 cells were treated with conditioned media from umbilical cord mesenchymal stem cells. Cell proliferation and apoptosis were detected with co-culture systems, MTT assay and DNA fragmentation assay; the protein expressions were determined with Western blotting and immunoflorescence staining. Results Conditioned media from hUC-MSCs could inhibit proliferation and induce apoptosis of tumor cells in a dose- and time-dependent manner. The proliferation inhibition rate increased from 12.87% to 50.98%, whereas the apoptosis rate increased from 10.1% to 49.67%. Immunoblot analysis showed that the expressions of p-Akt and p-GSK-3β were down-regulated. Conclusion The hUC-MSCs conditioned media may suppress the growth of HCCC-9810 human cholangiocarcinoma cell line via PI3K/Akt pathway.

Key words: Akt pathway, Umbilical cord mesenchymal stem cells, Cholangiocarcinoma

中图分类号:

R735.7

刘娟, 韩国庆, 刘慧, 秦成勇. 人类脐带间充质干细胞抑制肝内胆管癌细胞生长的机制[J]. 山东大学学报（医学版）, 2014, 52(8): 1-5.

LIU Juan, HAN Guoqing, LIU Hui, QIN Chengyong. Mechanism of human umbilical cord mesenchymal stem cells suppressing cholangiocarcinoma cell growth[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(8): 1-5.

参考文献

[1] Yamada N, Yokoyama S, Kitamoto S, et al. Pathobiological implications of MUC16/CA125 expression in intrahepatic cholangiocarcinoma-mass forming type [J]. Pathobiology, 2012, 79(2):101-106.
[2] Blechacz B, Gores G J. Cholangiocarcinoma:advances in pathogenesis, diagnosis, and treatment [J]. Hepatology, 2008, 48:308-321.
[3] Pittenger M F, Mackay A M, Beck S C, et al. Multilineage potential of adult human mesenchymal stem cells [J]. Science, 1999, 284(5411):143-147.
[4] Pittenger M F, Martin B J. Mesenchymal stem cells and their potential as cardiac therapeutics [J]. Circ Res, 2004, 95(1):9-20.
[5] 马欣, 薛改, 刘建芳, 等. 肝匀浆上清液诱导人脐带间充质干细胞分化为肝样细胞[J]. 中国组织工程研究, 2013, 17(45):7877-7884.
[6] 闫俊卿, 韩涛, 朱争. 人脐带间充质干细胞生物学特性及向类肝细胞的分化[J]. 世界华人消化杂志, 2008, 16(15):1639-1644.
[7] 野向阳, 李相军, 徐岩, 等. 人脐带间充质干细胞体外成骨及其免疫学特征[J]. 中国组织工程研究与临床康复, 2009, 13(36):7029-7033.
[8] 郝晓娟, 朱旅云. 缺氧预处理脐带间充质干细胞诱导分化为内皮样细胞[J]. 中国组织工程研究, 2013, 17(45):7869-7876.
[9] Khakoo A Y, Pati S, Anderson S A, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a modeI of Kaposi's sarcoma [J]. J Exp Med, 2006, 203(5):1235-1247.
[10] 刘华, 陈亚娜, 郑燕, 等. 人脐带间充质干细胞对宫颈癌Hela细胞增殖的影响[J]. 山东大学学报:医学版, 2013, 51(6):29-33.
[11] Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model [J]. Cell Res, 2008, 18(4):500-507.
[12] Liu J, Han G, Liu H，et al. Suppression of cholangiocarcinoma cell growth by human umbilical cord mesenchymal stem cells:a possible role of Wnt and Akt signaling [J]. PLoS One, 2013, 8(4):e62844. doi:10.1371/journal.pone.0062844.
[13] Karnoub A E, Dash A B, Vo A P, et al. Mesenchymal stem cells within tumor stroma promote breast cancer metastasis [J]. Nature, 2007, 449(7162):557-563.
[14] Nakamizo A, Marini F, Amano T, et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas [J]. Cancer Res, 2005, 65(8):3307-3318.
[15] Lu Y R, Yuan Y, Wang X J, et al. The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo [J]. Cancer Biol Ther, 2008, 7(2):245-251.
[16] Prockop D J. Marrow stromal cells as stem cells for nonhematopoietic tissues [J]. Science, 1997, 276(5309):71-74.
[17] Schmitz K J, Lang H, Wohlschlaeger J, et al. AKT and ERK1/2 signaling in intrahepatic cholangiocarcinoma [J]. World J Gastroenterol, 2007, 13 (48):6470-6477.
[18] Fang D, Hawke D, Zheng Y, et al. Phosphorylation of β-catenin by AKT promotes β-catenin transcriptional activity [J]. J Biol Chem, 2007, 282(15):11221-11229.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed

人类脐带间充质干细胞抑制肝内胆管癌细胞生长的机制

Mechanism of human umbilical cord mesenchymal stem cells suppressing cholangiocarcinoma cell growth

PDF (PC)

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 4

多维度评价

本文评价

推荐阅读 0

[1]	王凯民,谭娟娟,严志强,李志强. Sirtuin在低氧诱导人脐带间充质干细胞增殖中的作用[J]. 山东大学学报（医学版）, 2017, 55(7): 23-30.
[2]	刘宁,吕欣,李栋,黄志伟,刘毅,张乐玲. 人血管生成素1基因慢病毒表达载体的构建及其在脐带间充质干细胞的表达[J]. 山东大学学报（医学版）, 2016, 54(12): 1-7.
[3]	王娜,陈乃耀. 脐带间充质干细胞对小胶质细胞增殖及活化的影响[J]. 山东大学学报（医学版）, 2016, 54(10): 16-20.
[4]	商笑1，崔元孝1，刘晓雨1，冯肖亚2. 人脐带间充质干细胞联合血肿抽吸术治疗大鼠脑出血的实验研究[J]. 山东大学学报(医学版), 2013, 51(10): 10-14.