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)