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Aim:To investigate whether paeonol (Pae) has synergistic effects with cisplatin(CDDP) on the growth-inhibition and apoptosis-induction of human hepatomacell lines HepG_2 and SMMC-7721.Methods:The cytotoxic effect of drugswas measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromideassay.The coefficient of drug interaction was used to analyze the nature of druginteractions.Morphological changes were observed by acridine orange fluo-rescence staining.Cell cycle and the apoptosis rate were detected by flowcytometry.Bcl-2 and Bax expression were assayed by immunohistochemicalstaining.Results:Pae or CDDP had antiproliferative effect on the 2 cell linesin a dose-dependent manner,with different sensitivities to drugs.Moreinterestingly,a synergistic inhibitory effect on the viability of the 2 cell lineswas observed after treatment with a combination of Pae (15.63,31.25,and 62.5mg/L) with various concentrations of CDDP.Further study showed typical mor-phological changes of apoptosis if the cells were exposed to the two agents for24 h.The apoptotic rate of the cells with combination treatment was signifi-cantly higher than that of cells treated with Pae or CDDP alone.The expressionof Bcl-2 decreased and that of Bax increased in the treated groups,especially inthe combination group,with the ratio of Bcl-2/Bax decreasing correspondingly.Additionally,a combination of Pae with CDDP resulted in a stronger S phasearrest,compared with Pae or CDDP alone.Conclusion:Pae,in combinationwith CDDP,had a significantly synergistic growth-inhibitory and apoptosis-in-ducing effect on the 2 human hepatoma cell lines,which may be useful inhepatoma treatment.
Aim: To investigate whether paeonol (Pae) has synergistic effects with cisplatin (CDDP) on the growth-inhibition and apoptosis-induction of human hepatoma cells line HepG_2 and SMMC-7721. Methods: The cytotoxic effect of drugs was measured by 3- (4, 5-dimethylthiazol-2-yl) -2,5-diphenyl-tetrazolium bromideassay. The coefficient of drug interaction was used to analyze the nature of druginteractions. Morphological changes were observed by acridine orange fluo-rescence staining. Cell cycle and the apoptosis rate were detected by flow cytometry. Bcl-2 and Bax expression were assayed by immunohistochemical stain. Results: Pae or CDDP had antiproliferative effect on the 2 cell lines in a dose-dependent manner, with different sensitivities to drugs. Moreinterestingly, a synergistic inhibitory effect on the viability of the 2 cell lineswas observed after treatment with a combination of Pae (15.63, 31.25, and 62.5 mg / L) with various concentrations of CDDP. Further studies showed typical mor-phological changes of apoptotic osis if the cells were exposed to the two agents for 24 h. apoptotic rate of the cells with combination treatment was signifi-cantly higher than that of cells treated with Pae or CDDP alone. the expression of Bcl-2 decreased and that of Bax increased in the treated groups, especially inthe combination groups, with the ratio of Bcl-2 / Bax decreased correspondingly. Additionally, a combination of Pae with CDDP resulted in stronger S phasearrest, compared with Pae or CDDP alone. Confluence: Pae, in combination with CDDP , had a significant synergistic growth-inhibitory and apoptosis-in-ducing effect on the 2 human hepatoma cell lines, which may be useful in hepatoma treatment.