刘佳玲,童陈琦.二甲双胍抑制胰腺癌干细胞生长的实验研究[J].肿瘤学杂志,2016,22(6):467-472. |
二甲双胍抑制胰腺癌干细胞生长的实验研究 |
Inhibition Effect of Metformin on the Growth of Pancreatic Cancer Stem Cells |
投稿时间:2015-11-18 |
DOI:10.11735/j.issn.1671-170X.2016.06.B007 |
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中文关键词: 二甲双胍 胰腺肿瘤 干细胞 凋亡 |
英文关键词:metformin pancreatic neoplasms stem cells apoptosis |
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中文摘要: |
摘 要:[目的] 探讨二甲双胍对胰腺癌干细胞的生长抑制作用。[方法] 利用无血清培养基的超低粘附培养方法获得干细胞球样胰腺癌PANC1细胞,然后通过定量PCR检测干细胞球样PANC1细胞中CD133及PDX-1的表达情况,验证胰腺癌干细胞;利用干细胞球样PANC1细胞的MTT实验、流式周期检测实验、Annexin-Ⅴ细胞凋亡实验、定量PCR凋亡因子检测实验,研究二甲双胍对干细胞球样PANC1细胞增殖、周期及凋亡的影响;借助干细胞球样PANC1胰腺癌细胞构建鼠移植瘤模型,观察二甲双胍对肿瘤生长的影响。[结果] 二甲双胍能够明显抑制干细胞球样胰腺癌PANC1细胞增殖,且具有浓度依赖性,最大抑制率为81.3%,半数有效抑制浓度IC50为(11.94±1.43)mmol/L;二甲双胍对干细胞球样PANC1细胞的G0/G1期有阻滞作用;二甲双胍可以诱导干细胞球样PANC1细胞凋亡,与空白对照组比较,二甲双胍组干细胞球样PANC1细胞的Bcl-2 mRNA减少,而Bad、Bax mRNA的表达增加;干细胞球样PANC1细胞接种至裸鼠皮下均能成瘤,且二甲双胍能够明显抑制移植瘤的生长。[结论] 二甲双胍能够抑制胰腺癌干细胞增殖,阻滞G0/G1期,并诱导胰腺癌干细胞凋亡,发挥抗胰腺癌干细胞生长的作用。 |
英文摘要: |
Abstract:[Objective] To observe the inhibition effect of metformin on the growth of pancreatic cancer stem cells. [Methods] Firstly,PANC1 cells were cultured with DMEM/F12K (serum-free,10ng/ml EGF,15ng/ml bFGF,2% B27 supplement) in 6-well ultra low attachment plates,to establish stem-like PANC1. We used qPCR to identify stem-like PANC1 cells through detecting the expression of CD133 and PDX-1. MTT,cell cycle,Annexin-Ⅴ apoptosis and qPCR detection of apoptosis factors were used to research the effect of metformin on proliferation,cell cycle and apoptosis of stem-like PANC1 cells. Mice transplanted tumor model of stem-like PANC1 cells was used to observe the effects of metformin on tumor growth. [Results] Metformin can significantly inhibit stem-like PANC1 cells proliferation with the concentration-dependence,the biggest inhibition rate was 81.3% and the IC50 was (11.94±1.43)mmol/L. Metformin induced G0/G1 phase retardation of stem-like PANC1 cells. Metformin also increased cell apoptosis of stem-like PANC1 cells,and Bcl-2 mRNA treated by metformin decreased.However,expression of Bax,Bad mRNA increased. Mice transplanted tumor model of stem-like PANC1 cells was successfully established,indicating stem-like PANC1 cells had a great tumorigenicity. Additionally,metformin could signifi-cantly inhibit the growth of transplanted tumor. [Conclusion] Metformin can inhibit the growth of pancreatic cancer stem cells by inhibiting stem-like PANC1 cells proliferation,blocking cell cycle and inducing cells apoptosis. |
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