Journal of Southern Medical University ›› 2014, Vol. 34 ›› Issue (01): 25-.
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Abstract: Objective To investigate the effect of 3-bromopyruvate (3-BP) in sensitizing hepatocellular carcinoma cells tocisplatin-induced apoptosis and its possible mechanism. Methods The growth inhibition of HepG2 and SMMC7721 cellsfollowing exposures to different concentrations of 3-BP and cisplatin was measured by MTT assay. The apoptosis of cellstreated with 100 μmol/L 3-BP with or without 8 μmol/L cisplatin was assessed using flow cytometry with PI staining, and theactivity of caspase-3 and intracellular ATP level were detected using commercial detection kits; the expression of XIAP andPARP was analyzed using Western blotting. Results 3-BP produced obvious inhibitory effects on HepG2 and SMMC7721 cellsat the concentrations of 50-400 μmol/L with IC50 values of 238.9 ± 13.9 μmol/L and 278.7 ± 11.7 μmol/L for a 48-h treatment,respectively. Cisplatin also inhibited the growth of HepG2 and SMMC7721 cells at the concentrations of 2-32 μmol/L, with IC50values of 16.4±0.9 μmol/L and 20.9±1.8 μmol/L after a 48-h treatment, respectively. Treatment with 100 μmol/L 3-BP combinedwith 8 μmol/L cisplatin for 48 h resulted in a growth inhibition rate of (60.6 ± 2.2)% in HepG2 cells and (56.8 ± 2.3)% inSMMC7721 cells, which were significantly higher than those in cells treated with 3-BP or cisplatin alone. The combinedtreatment for 48 h induced an apoptotic rate of (51.1±4.3)% in HepG2 cells and (46.5±3.9)% in SMMC7721 cells, which were alsomarkedly higher than those in cells with 3-BP or cisplatin treatment alone. Conclusion 3-BP can sensitize HepG2 andSMMC7721 cells to cisplatin-induced apoptosis possibly by causing intracellular ATP deficiency, down-regulating XIAP, andincreasing caspase-3 activity.
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https://www.j-smu.com/EN/Y2014/V34/I01/25