Objective      To investigate the effect of glycolytic inhibitor 3-bromopyruvate(3-BrPA) combined with cisplatin on inhibiting lung cancer A549 cells and its possible mechanism.       Methods      The cell proliferation of A549 cell streated with different concentrations of 3-BrPA and/or cisplatin was detected by CCK-8 assay. 3-BrPA w

ith concentration of 40 μmol/L

which is lower than the median inhibitory concentration (IC

50

)

was selected to combine with cisplatin(1 mg/L) to treat A549 cells. Then

an inverted microscope was used to observe the morphological changes of A549 cells

and flow cytometry was used to detect apoptosis. The A549 cells were treated with different concentrations of 3-BrPA

and then flow cytometry was adopted to detect the changes of cell cycle.The intracellular hexokinase activity was detected with hexokinase activity assay kit.       Results      Compared with the control group

3-BrPA with concentration higher than 20 μmol/L showed significantly inhibitory effect on A549 cells (P0.01). Compared with cisplatin alone

3-BrPA in combination with cisplatin significantly enhanced the toxic effect of cisplatin on A549 cells (P0.01). After A549 cells were treated with 3-BrPA for 48 h

the morphological changes of cell apoptosis were observed. The combination group showed more obvious morphological changes

and some cells showed signs of necrosis. Flow cytometry indicated that compared with the control group

the apoptotic rates of the 3-BrPA alone group

cisplatin alone group and combination group were significantly higher (P0.01).The apoptotic rates of the 3-BrPA along group and cisplatin alone group were significantly lower than that of the combination group (P0.01). The cell cycle assay results showed that 3-BrPA arrested A549 cells at G

1

phase. Hexokinase activity test showed that compared with the control group

the hexokinase activity of 3-BrPA group was significantly lower (P0.01).       Conclusion      3-BrPA can inhibit the proliferation of A549 cells and induce apoptosis

and its combination with cisplatin shows better effect than single treatment

indicating that 3-BrPA has chemotherapy sensitizing effect. The mechanism may be related with inhibiting cancer cell glycolysis

and thus affecting the cancer cell energy metabolism.