期刊文献+

二甲双胍抑制肝癌MHCC97-H细胞迁移及侵袭活性的实验研究

Inhibitory effect of metformin on invasion and migration activity of liver cancer cell line MH-CC97-H
原文传递
导出
摘要 目的观察二甲双胍对人肝癌细胞在体外和裸鼠体内转移的抑制作用及其相关机制。方法选用三个组:A组(二甲双胍5mmoL/L)、B组(顺铂5mg/L)和C组(DMEM空白对照组)。用细胞划痕实验及Transwell小室法检测细胞的迁移及侵袭能力,逆转录-聚合酶链反应(RT—PCR)及Westernblot法检测细胞中基质金属蛋白酶-2(MMP-2)、MMP-9mRNA及蛋白的表达水平;将MHCC97-H细胞接种于裸鼠,观察不同浓度的二甲双胍对裸鼠皮下瘤生长及转移的影响。结果对MHCC97-H细胞作用48h后,A、B两组细胞的迁移速率分别为(33.24±8.7)wm/h、(29.5±5.6)jxm/h,侵袭穿膜细胞数分别为(22.24±7.3)个、(18.24±4.6)个,MMP-2、MMP-9mRNA及蛋白表达均较c组明显降低,差异均有统计学意义(P〈0.01);药物处理组裸鼠皮下瘤的重量显著小于对照组,所有实验组肝脏转移瘤的大小和数量比较差异无统计学意义。结论二甲双胍能够抑制肝癌MHCC97-H细胞的迁移与侵袭,其机制可能与MMP-2、MMP-9表达下调有关,但转移抑制作用在动物体内却没有显现。 Objective To evaluate the inhibition effect and related mechanisms of mefformin on migration of human liver cancer cells in vitro and nude mice. Methods Three groups were selected to treat MHCC97-H cells, group A (Metformin 5 mmol/L), group B (Cisplatin 5 rag/L) as experimental group ,and group C (DMEM) as control group. Cell migration and invasion of MHCC97-H cell inhibited by metformin were assessed by migration experiment and transwell technique. Expression of MMP-2, MMP-9 gene in MHCC97-H ceils were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. Nude mice were transplanted with MHCC97-H cells, and tumor growth in- hibition was detected. Results The number of migration and invasion of MHCC97-H cells were significantly higher in the control group than those in the Metformin group. A significant down-regulation of expression of MMP-2, MMP-9 mRNA and protein levels were observed in MHCC97-H cells when metformin was given after 48 h,tumor size in the mefformin-treated group was significantly smaller than that in the control group. How- ever, the size and number of metastatic tumors in all groups had no significant difference. Conclusions Met- formin is able to inhibit the cell invasion and migration of MHCC97-H cells by down-regulating the MMP-2, MMP-9 mRNA and protein expression, while this metastatic inhibition does not show in vivo.
出处 《中国实用医刊》 2013年第15期1-3,共3页 Chinese Journal of Practical Medicine
基金 卫生部重大传染病防治重大科技专项基金(卫科传专项[2009]3号编号:2008Ex10002019)
关键词 二甲双胍 MHCC97-H 基质金属蛋白酶-2 基质金属蛋白酶-9 肿瘤侵袭转移 Mefformin MHCC97-H Matrix metalloproteinase-2 Matrix metalloproteinase-9 Neoplastic invasion and metastasis
  • 相关文献

参考文献16

  • 1Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002[J]. CA Cancer J Clin,2005,55(2) :74-108.
  • 2Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes[J]. Diabetes Care, 2009, 32(9) :1620-1625.
  • 3Evans JM, Donnelly LA, Emslie-Smith AM, et al. Metformin and re- duced risk of cancer indiabetic patients [ J ] . BMJ, 2005, 330 (7503) : 1304-1305.
  • 4Libby G, Donnelly LA, Donnan PT, et al. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes[ J]. Diabetes Care ,2009, 32 (9) : 1620-1625.
  • 5Hirsch HA, Iliopoulos D, Tsichlis PN, et al. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor Growth and prolong remission [ J]. Cancer Res, 2009, 69 (19) :7507-7511.
  • 6Buzzai M, Jones RG. Systemic treatment with antidiabetic drug met- formin selectively impairs p53-deficient tumor cell growth [ J]. Cancer Res, 2007,67 ( 14 ) : 6745-6752.
  • 7Ben Sahra I, Laurent K. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level [ J ]. Oncogene,2008,27 ( 25 ) : 3576-3586.
  • 8卢清军,熊宇,严威,林芬,王效民,吴国洋.二甲双胍对肝癌细胞增殖及凋亡相关基因表达的影响[J].中华实验外科杂志,2011,28(7):1107-1110. 被引量:8
  • 9Hwang YP, Jeong HG. Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase Calpha-dependent pathway: phor- bol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/ activator pmtein-l[J]. Br J Pharmacol, 2010, 160(5):1195-1211.
  • 10Rattan R, Graham RP, Maguire JL, et al. Metformin suppresses o- varian cancer growth and metastasis with enhancement of cisplatin cy- totoxicity in vivo[ J]. Neoplasia, 2011, 13 (5) :483-491.

二级参考文献4

共引文献7

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部