| 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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