Synergistically Antiproliferative Effect Of Paeonol And Cisplatin On Human Esophageal Cancer Cell Lines And The Possible Mechanism

Objective To investigate the growth-inhibitory effect of Paeonol with cisplatin in human esophageal cancer cell lines Eca-109 and SEG-1 and the possible mechanism, in order to develop an effective therapy for esophageal cancer.Methodsâ‘ The antiproliferative effect of Paeonol on Eca-109 and SEG-1 cell lines in vitro was measured by MTT assay.â‘¡To investigate the synergistically inhibitory effects of Paeonol and cisplatin on the proliferation of Eca-109 and SEG-1 cell lines, three doses of Paeonol (7.81,15.63,31.25 mg·L^-1) were used to combine with cisplatin. The coefficient of drug interaction (CDI) was used to analyse the synergistically inhibitory effect of drug combination.â‘¢Acridine orange fluorescence staining, Flow Cytometry analysis and immunocytochemical stain for Bcl-2/Bax were used to analyse Possible mechanisms of the synergistic antiproliferation effect of Paeonol in combination with cisplatin.Resultsâ‘ Paeonol at concentrations of 7.81²50mg·L^-1, had inhibitory effect on the proliferation of both Eca-109 and SEG-1 cells, which suggested obvious dose-dependent manner of Pae. The r values of dose-effect curves for single-agent Pae on both Eca-109 and SEG-1 cell lines were 0.889 and 0.961 respectively. The IC50 values were 124.77 mg?L-1 (Eca-109) and 57.73 mg?L-1 (SEG-1).â‘¡Paeonol combining with cisplatin showed synergistically inhibitory effect on the proliferation of the two cell lines in appropriate concentrations.â‘¢Paeonol combined with cisplatin had synergistic apoptosis induction effect on the two cell lines. We also found that Paeonol can induced cell cycle arrest at the S phase in the two human esophageal cancer cell lines, along with the decrease in the population of G0/G1 phase cells. S-P method was used to examine the expression of Bcl-2 and Bax, which suggested up- or down-regulation of Bcl-2 protein family by Pae and/or CDDP might be the mechanism of apoptosis.Conclusion The results in the present study demonstrated that Paeonol has antiproliferative effect on the human esophageal cancer cell lines Eca-109 and SEG-1, with an obvious dose-dependent manner. Paeonol combined with cisplatin had a significantly synergistically growth-inhibitory effect on the two cell lines, which may be related with the apoptosis-inducing and cell cycle arrest effect. Further research found the effect of Pae and/or CDDP on expression of Bcl-2 protein family might be the mechanism of apoptosis.