2019年第46卷第4期目录
|
|
封面故事:糖代谢是肿瘤细胞获取ATP的主要途径,包括糖酵解和氧化磷酸化两个途径.在肿瘤细胞的发生发展过程中,绝大多数肿瘤细胞主要依赖糖酵解提供ATP,氧化磷酸化只是一种辅助代谢途径.研究发现,巨噬细胞集落刺激因子(M-CSF)可提高巨噬细胞的糖摄取能力,但肿瘤细胞 M-CSF的表达与糖代谢之间的具体联系尚不明确.田云等通过构建稳定转染M-CSF的乳腺癌MCF-7细胞发现,PI3K/AKT信号通路参与胞质M-CSF活化MCF-7细胞糖酵解的过程,胞质M-CSF通过上调HK2、PKM2和GLUT-1的表达,增加葡萄糖摄取,促进ATP的产生,从而产生化疗药物5-FU抵抗,使乳腺癌细胞生存能力得到极大增强.本研究展示了胞质M-CSF促进糖酵解的一面,为研发能够靶向抑制乳腺癌相关糖酵解酶或ATP的抗癌药物提供了实验依据,具有一定的参考意义.
(田 云,刘臻,宁倩,莫中成,张蒙夏,唐圣松. 巨噬细胞集落刺激因子经PI3K/AKT信号途径影响人乳腺癌MCF-7细胞糖代谢,本期第398~405页)
Cover Story:To explore the effect and mechanisms of cytoplasmic M-CSF on glucose metabolism in human breast cancer MCF-7 cells, MCF-7 cells stable expressing cytoplasmic M-CSF were constructed. Relative ATP content was measured by ATP assay kit, glucose was measured using glucose assay kit and lactate was measured using lactate acid assay kit. The expression of HK2, PKM2 and GLUT-1 in three kinds of cell with LY294002 or API-2 was detected by West-blotting. The sensitivity of MCF-7 and MCF-7-M cells to 5-FU with the treatment of ATP depletion by 3-BrPA was observed by MTT assay. It was found that the ATP level of MCF-7-M cells was significantly higher than that of MCF-7 cells (P<0.05); 2-DG decreases the ATP level of MCF-7 and MCF-7-M cells, and the effect of lowering the ATP level of MCF-7-M cells is more obvious (P<0.01). The glucose uptake and lactate secretion of MCF-7-M cells were significantly higher than those of MCF-7 cells (P<0.01). After the treatment with API-2, the glucose consumption and lactate secretion of MCF-7 and MCF-7-M cells were significantly reduced (P<0.01). The expressions of GLUT-1, HK2 and PKM2 in MCF-7-M cells were significantly higher than those in MCF-7 cells (P<0.01). Both LY294002 and API-2 inhibited the expression of GLUT-1 in MCF-7-M cells (P<0.05). After the treatment with 3-BrPA, the drug sensitivity of MCF-7-M and MCF-7 cells to 5- FU was significantly enhanced (P<0.01). In conclusion, cytoplasmic M-CSF activates glycolysis by induce GLUT-1, HK2 and PKM2 protein expression in MCF-7 cells; PI3K/AKT signaling involves the pathway that glycolysis was activated by cytoplasmic M-CSF in MCF-7 cells.
|
综述与专论
研究报告
技术与方法
|
|