二甲双胍对结肠癌细胞增殖的影响

doi:10.3877/cma.j.issn.2095-3224.2018.03.009

中华结直肠疾病电子杂志 ›› 2018, Vol. 07 ›› Issue (03) : 242 -245. doi: 10.3877/cma.j.issn.2095-3224.2018.03.009

所属专题：文献；

论著

二甲双胍对结肠癌细胞增殖的影响

张斯萌¹, 张晔¹, 车晓芳¹, 曲秀娟¹, 刘云鹏¹^,^†(

)

^1. 110001　沈阳，中国医科大学附属第一医院肿瘤内科

收稿日期:2017-05-19 出版日期:2018-06-25
通信作者: 刘云鹏
基金资助:
国家自然科学基金面上项目(No.81372546); 辽宁省科学技术计划项目(No.2014226033，No.2014225013); 辽宁省中央引导地方科技发展专项资金(No.2016007010)

The influence of metformin on colon cancer cell growth

Simeng Zhang¹, Ye Zhang¹, Xiaofang Che¹, Xiujuan Qu¹, Yunpeng Liu¹^,^†()

^1. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China

Received:2017-05-19 Published:2018-06-25
Corresponding author: Yunpeng Liu
About author:
Correspondence author: Liu Yunpeng, Email: cmuliuyunpeng@hotmail.com

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目的

研究发现，二甲双胍在多种肿瘤中显示出抗肿瘤作用。在结直肠癌中，二甲双胍对肿瘤的抑制作用机制尚不明确，本研究旨在探究二甲双胍对结肠癌细胞增殖的影响。

方法

MTT实验检测不同浓度的二甲双胍对HT29结肠癌细胞增殖率变化的影响。利用蛋白免疫印迹方法检测二甲双胍作用下的HT29结肠癌细胞增殖相关蛋白表达的变化。

结果

二甲双胍能够抑制结肠癌HT29细胞的增殖且呈浓度依赖性。利用二甲双胍处理HT29细胞不同时间点后发现，二甲双胍能够抑制蛋白激酶B（Akt）与细胞外调节蛋白激酶（ERK）的磷酸化水平。进一步研究证实，二甲双胍能够抑制结肠癌细胞Akt、Erk上游IGF1R磷酸化水平。

结论

二甲双胍能够通过阻断胰岛素样生长因子受体（IGF1R）进而抑制下游Akt、Erk信号抑制结肠癌HT29细胞增殖。

关键词: 结直肠肿瘤, 二甲双胍, 细胞增殖, MTT实验, 蛋白免疫印迹方法

Objective

The antitumor effect of metformin have been explored in various type of cancers. In colorectal cancer, the mechanism of inhibition effect of metformin is unclear. Thus, the purpose of the present study is to investigate the effect of metformin on proliferation of colon cancer cells.

Methods

The variation of proliferation rate of HT29 colon cancer cell line was detected by MTT assay. Western Blotting assay was performed to test the variation of protein expression level in metformin treated HT29 cells.

Results

Metformin could inhibit proliferation of HT29 cells which present concentration dependence. After metformin treated HT29 cells for different duration, protein kinase B (Akt) and extracellular regulated protein kinases (Erk) phosphorylation were down-regulated. Further investigation showed that metformin could inhibit insulin-like growth factor 1 receptor (IGF1R) phosphorylation level which is the upstream of Akt and Erk signaling pathway in HT29 cells.

Conclusion

Metformin inhibit proliferation of HT29 colon cancer cell by blocking IGF1R and downstream Akt and Erk signaling pathway.

Key words: Colorectal neoplasms, Metformin, Cell proliferation, MTT assay, Western blotting assay

图3 二甲双胍（5 mmol/L）作用HT29细胞0、24、48 h后，对p-IGF1R，IGF1R与Actin蛋白表达的影响

[1]	Chen W, Zheng R, Baade PD, et al.Cancer statistics in China, 2015 [J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[2]	Coyle C, Cafferty FH, Vale C, et al.Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis [J]. Ann Oncol, 2016, 27(12): 2184-2195.
[3]	Jiralerspong S, Palla SL, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer [J]. J Clin Oncol, 2009, 27(20): 3297-3302.
[4]	Chen TM, Lin CC, Huang PT, et al. Metformin associated with lower mortality in diabetic patients with early stage hepatocellular carcinoma after radiofrequency ablation [J]. J Gastroenterol Hepatol, 2011, 26(5): 858-865.
[5]	Garrett CR, Hassabo HM, Bhadkamkar NA, et al. Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer [J]. Br J Cancer, 2012, 106(8): 1374-1378.
[6]	Mc Menamin UC, Murray LJ, Hughes CM, et al. Metformin use and survival after colorectal cancer: A population-based cohort study [J]. Int J Cancer, 2016, 138(2): 369-379.
[7]	周小智, 薛耀明, 朱波，等. 二甲双胍对人结肠癌细胞株SW-480增殖的影响 [J]. 南方医科大学学报, 2010, 30(8): 1935-1938, 1942.
[8]	Pollak M. Insulin and insulin-like growth factor signalling in neoplasia [J]. Nat Rev Cancer, 2008, 8(12): 915-928.
[9]	Adachi Y, Lee CT, Coffee K, et al. Effects of genetic blockade of the insulin-like growth factor receptor in human colon cancer cell lines [J]. Gastroenterology, 2002, 123(4): 1191-1204.
[10]	Shackelford DB, Abt E, Gerken L, et al. LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin [J]. Cancer Cell, 2013, 23(2): 143-158.
[11]	Faubert B, Boily G, Izreig S, et al. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo [J]. Cell Metab, 2013, 17(1): 113-124.
[12]	Morales DR, Morris AD. Metformin in cancer treatment and prevention [J]. Annu Rev Med, 2015, 66: 17-29.

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The influence of metformin on colon cancer cell growth

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