引用本文:[点击复制]
[点击复制]
【打印本页】 【在线阅读全文】【下载PDF全文】 查看/发表评论下载PDF阅读器关闭

←前一篇|后一篇→

过刊浏览    高级检索

本文已被:浏览 69次   下载 19 本文二维码信息
码上扫一扫!
2-脱氧葡萄糖对乳腺癌MCF7/ErbB2细胞增殖 迁移和侵袭的影响
申越,贺丽,李华,陈璟若,徐硕,赵玉华
0
(华西基础医学与法医学院人体解剖学教研室,华西基础医学与法医学院生物化学与分子生物学教研室;华西药学院微生物与生化药学教研室;华西基础医学与法医学院生物化学与分子生物学教研室,)
摘要:
目的 探讨糖酵解抑制剂2-脱氧葡萄糖(2-Deoxy-D-glucose,2-DG)对乳腺癌MCF7/ErbB2细胞增殖、迁移和侵袭的影响及其分子机制。方法 用不同浓度的2-DG(0, 05, 1, 2, 4, 8, 16, 32 mM)处理MCF7/ErbB2细胞48h后,用MTS试剂盒测定细胞的增殖;用Transwell实验检测不同浓度2-DG(0, 0.5, 1, 2 mM)对MCF7/ErbB2细胞的迁移和侵袭的影响;用不同浓度2DG(0, 0.5, 1, 2 mM)处理MCF7/ErbB2细胞48h后,用葡萄糖和乳酸检测试剂盒分别测定培养基中的葡萄糖浓度和乳酸浓度,并计算细胞对葡萄糖的摄取量和乳酸生成量;用1 mM 2DG处理MCF7/ErbB2细胞0、4、8、12、24h后,用Western blot检测己糖激酶II(hexokinase II,HKII)蛋白表达水平。结果 与2-DG未处理组比较,2-DG(0.5~32 mM)能抑制MCF7/ ErbB2细胞的增殖;2-DG(0.5, 1, 2 mM)能显著抑制MCF7/ ErbB2细胞的迁移和侵袭(P<0.001),同时显著降低葡萄糖摄取量和乳酸生成量(P<0.001),而且上述抑制作用均表现出对2-DG剂量的依赖性;1 mM 2-DG 显著下调MCF7/ ErbB2细胞中HKII的蛋白水平。结论 2-DG通过下调HKII蛋白表达降低糖酵解水平,从而抑制乳腺癌MCF7/ ErbB2细胞的增殖、迁移和侵袭。
关键词:  2-脱氧葡萄糖  乳腺癌  增殖  迁移  侵袭  糖酵解
DOI:
基金项目:国家自然科学基金(81272907);四川省科技厅应用基础研究项目(2016JY0143)
Effect of 2-DG on proliferation migration and invasion of breast cancer cell line MCF7/ErbB2
SHEN Yue,HE Li,LI Hua,CHEN Jingruo,XU Shuo,ZHAO Yuhua
(Department of Anatomy,West China School of Basic Medical Sciences and Forensic Medicine,Sichuan University,Department of Biochemistry and Molecular Biology,West China School of Basic Medical Sciences and Forensic Medicine,Sichuan University;Department of Microbiology and Biochemical Pharmacy,West China School of Pharmacy Sichuan University)
Abstract:
Objective To investigate the effect of glycolysis inhibitor 2-DG on proliferation, migration and invasion of ErbB2 overexpressing breast cancer cell line MCF7/ ErbB2 and its molecular mechanism. Methods MCF7/ ErbB2 cells were treated with 2-DG (0, 0.5, 1, 2, 4, 8, 16, 32 mM) for 48 hours. Cell proliferation was detected by MTS assay. MCF7/ ErbB2 cells were treated with different concentration of 2-DG (0, 0.5, 1, 2 mM) for 24 hours. Cell migration and invasion was detected by Transwell assays. The glucose and lactate concentration in the culture media were determined by glucose and lactate assay kit, respectively, when MCF7/ ErbB2 cells were treated with 2-DG (0, 0.5, 1, 2 mM) for 48 hours, and then glucose uptake and lactate production by the cells were calculated. Finally, the cells were treated with 21 mM DG for different times (0, 4, 8, 12, 24 hours) to detect hexokinase II (HKII) protein levels by Western blot. Results Compared with untreated group, 2-DG ( 0.5-32 mM) significantly decreased the proliferation of MCF7/ ErbB2, 2-DG (0.5,1,2 mM) also inhibits the migration, invasion, glucose uptake and lactate production of MCF7/ ErbB2 cells (P<0.001). Inhibition of cell proliferation, migration, invasion and glycolysis was 2-DG dose dependent. Moreover, 1 mM 2-DG downregulated HKII protein levels in MCF7/ ErbB2 cells significantly. Conclusion In breast cancer cell line MCF7/ ErbB2, 2-DG inhibits glycolysis by downregulating HKII protein levels leading to inhibition of proliferation, migration and invasion.
Key words:  2-Deoxyglucose  Breast cancer  Proliferation  Migration Invasion  Glycolysis

用微信扫一扫

用微信扫一扫