Effect of glibenclamide on viability and acid-base equilibrium of glioblastoma cells
10.3969/j.issn.1000-4718.2017.08.010
- VernacularTitle:格列本脲对胶质母细胞瘤活性及细胞内酸碱平衡的影响
- Author:
Ling GUO
;
Huajun SHENG
;
Qian LIU
;
Qinghua YANG
;
Shujuan ZHU
- Keywords:
Glibenclamide;
Glioblastoma;
Cell viability
- From:
Chinese Journal of Pathophysiology
2017;33(8):1405-1410
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effect of glibenclamide (Glib) on the viability and acid-base equilibrium of glioblastoma cells.METHODS: U251 cells and U87 cells were treated with Glib at different concentrations.The inhibitory rates were detected by CCK-8 assay.The effective dose was screened and the experiment was divided into control group and drug treatment groups.The migration ability was monitored by wound healing assay, and intracellular pH was detected by pH indicator fluorescent probe.The protein expression levels of inwardly-rectifying potassium channel 4.1 (Kir4.1) and monocarboxylate transport protein 1 (MCT1) were determined by Western blot.RESULTS: The half maximal inhibitory concentrations (IC50) of Glib for 48 h exposure of U251 cells and U87 cells were 400.20 μmol/L and 553.70 μmol/L, respectively.The effective inhibition doses of Glib for U251 cells were from the ranges of 100 μmol/L to 1 600 μmol/L, and those for U87 cells were from 50 μmol/L to 1 600 μmol/L in a concentration-dependent manner (P<0.05).Glib not only inhibited the migration (P<0.05) of U251 cells and U87 cells, which was negatively correlated with drug concentration (P<0.05), but also reduced the intracellular fluorescence intensity in experimental group (P<0.05), suggesting that with the increase in drug concentration, the intracellular pH decreased gradually (P<0.05).The protein expression of Kir4.1 and MCT1 was down-regulated by treatment with Glib, and was negatively correlated with concentration of Glib.CONCLUSION: Glib, a kind of potassium channel blocker, induces intracellular acidification via down-regulating the expression of Kir4.1 and MCT1, thus inhibiting the growth of glioblastoma in a certain dose range.
