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高浓度二甲双胍通过JNK通路抑制MIN6细胞增殖和迁移

High-concentration metformin inhibits the proliferation and migration of MIN6 cells through JNK signaling pathway

来源期刊: 广州医药 | 1-4 发布时间:2021-12-01 收稿时间:2025/11/13 17:24:31 阅读量:42
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关键词:
二甲双胍MIN6细胞凋亡JNK
MetforminMIN6ApoptosisJNK
DOI:
10.3969/j.issn.1000-8535.2018.01.001
收稿时间:
2017-08-30 
修订日期:
 
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引用总数:
0  
目的 本研究从细胞生物学角度检测二甲双胍对小鼠胰岛瘤MIN6的影响,并探讨此过程中包含的分子生物学机制。方法 MTT法检测不同浓度二甲双胍(1、2、5、10、20 mmol/L)对MIN6细胞活力的影响,细胞划痕实验检测二甲双胍对MIN6细胞迁移的影响,免疫印记实验检测此过程中细胞凋亡相关蛋白Bcl-2、Bax、caspase3表达的变化,及AMPK和JNK信号通路蛋白磷酸化水平的变化。结果 二甲双胍浓度大于10 mmol/L时可以抑制MIN6细胞的活力(P<0.01),降低其迁移能力(P<0.01),高浓度二甲双胍可以上调细胞内凋亡蛋白Bax(P<0.05)和p-AMPK的表达(P<0.05),降低抗凋亡蛋白Bcl-2的表达,增加caspase3剪切体(P<0.05)。同时,二甲双胍可以降低MIN6细胞内JNK信号通路的磷酸化水平(P<0.05)。结论 高浓度二甲双胍可以抑制MIN6细胞的增殖和迁移,其作用可能与降低了JNK信号的通路活化有关。
Objective This study aims to investigate the effect of metformin on proliferation and migration of MIN6 cells, and to explore the underlying mechanism. Methods The viability of MIN6 cells that were treated with various metformin (1,2,5,10 and 20 mmol/L) was detected by MTT assay. The migration of MIN6 cells was determined by wound-healing assay. Meanwhile, the proteins expression of Bcl-2, Bax, caspase3 and the phosphorylation of AMPK, JNK was detected by western bolt assay. Results The cell viability and the migration of MIN6 cells were decreased when the concentration of metformin above 10 mmol/L(P<0.01). The expression of apoptosis-related protein Bax(P<0.05) and p-AMPK(P<0.05)was up-regulated, anti-apoptosis-related protein Bcl-2 was down-regulated and cleaved caspase3 (P<0.05)was increased after high metformin treatment. At the same time, the phosphorylation of JNK was down-regulated by metformin(P<0.05). Conclusion High concertration of metformin may inhibit the proliferation and migration of MIN6 cells through suppressing the activation of JNK signaling pathway.
1、 HWANG Y, JEONG H. Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase C alpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1[J]. Br J Pharmacol, 2010, 160(5):1195-1211. HWANG Y, JEONG H. Metformin blocks migration and invasion of tumour cells by inhibition of matrix metalloproteinase-9 activation through a calcium and protein kinase C alpha-dependent pathway: phorbol-12-myristate-13-acetate-induced/extracellular signal-regulated kinase/activator protein-1[J]. Br J Pharmacol, 2010, 160(5):1195-1211.
2、 XIE W, WANG L, SHENG H, et al. Metformin induces growth inhibition and cell cycle arrest by upregulating microRNA34a in renal cancer cells[J]. Med Sci Monit, 2017(23):29-37. XIE W, WANG L, SHENG H, et al. Metformin induces growth inhibition and cell cycle arrest by upregulating microRNA34a in renal cancer cells[J]. Med Sci Monit, 2017(23):29-37.
3、 WANG X W, HU S, LIANG Q, et al. Activation of c-jun N-terminal kinase in spinal cord contributes to breast cancer induced bone pain in rats[J]. Mol Brain, 2012, 5(1):1-7. WANG X W, HU S, LIANG Q, et al. Activation of c-jun N-terminal kinase in spinal cord contributes to breast cancer induced bone pain in rats[J]. Mol Brain, 2012, 5(1):1-7.
4、 HSIEH S, TSAI J, YANG S, et al. Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression[J]. Amino Acids, 2014, 46(12):2809-2822. HSIEH S, TSAI J, YANG S, et al. Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression[J]. Amino Acids, 2014, 46(12):2809-2822.
5、 ARIAANS G, JALVING M, VRIES E, et al. Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells[J]. BMC Cancer, 2017, 17(1):232. ARIAANS G, JALVING M, VRIES E, et al. Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells[J]. BMC Cancer, 2017, 17(1):232.
6、 GAO Z, LIU Z, BI M, et al. Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro[J]. Exp Ther Med, 2016, 11(5):1700-1706. GAO Z, LIU Z, BI M, et al. Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro[J]. Exp Ther Med, 2016, 11(5):1700-1706.
7、 SHI Y, HE Z, JIA Z, et al. Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer cells in vitro and in vivo[J]. Mol Med Rep, 2016, 14(4):2921-2928. SHI Y, HE Z, JIA Z, et al. Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer cells in vitro and in vivo[J]. Mol Med Rep, 2016, 14(4):2921-2928.
8、 LUO Q, HU D, HU S, et al. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma[J]. BMC Cancer, 2012, 12(1):517. LUO Q, HU D, HU S, et al. In vitro and in vivo anti-tumor effect of metformin as a novel therapeutic agent in human oral squamous cell carcinoma[J]. BMC Cancer, 2012, 12(1):517.
9、 JIANG Y, HUANG W, WANG J, et al. Metformin plays a dual role in MIN6 pancreatic β cell function through AMPK-dependent autophagy[J]. Int J Biol Sci, 2014, 10(3):268-277. JIANG Y, HUANG W, WANG J, et al. Metformin plays a dual role in MIN6 pancreatic β cell function through AMPK-dependent autophagy[J]. Int J Biol Sci, 2014, 10(3):268-277.
10、 SHAW R J. Metformin trims fats to restore insulin sensitivity[J]. Nat Med, 2013, 19(12):1570-1572. SHAW R J. Metformin trims fats to restore insulin sensitivity[J]. Nat Med, 2013, 19(12):1570-1572.
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