Abstract: Objective: To investigate the effect of oligomeric proanthocyanidins from grape seeds (O-GSP) combined with cisplatin (DDP) on the proliferation, cell cycle and cell cycle-related protein expression of A549 cells. Methods: A549 cells were cultured in vitro. The effects of DDP and O-GSP alone and in combination on the survival rate of A549 cells were observed by MTT assay; the combined effect of O-GSP and DDP on the cell cycle of A549 cells was detected by flow cytometry and the expression levels of the cell cycle-related proteins CDK 4, Cyclin D1 and p-Rb were detected by Western blot. Results: DDP (≥ 5 mg/L) and O-GSP (≥16 mg/L) treatments alone could inhibit A549 cell proliferation. The combined treatment had a synergistic effect on the inhibition of cell proliferation. DDP treatment alone at 5 mg/L arrested A549 cells at S phase and O-GSP at 4 mg/L arrested the cells at G0/G1 phase. The combination of DDP at 5 mg/L and O-GSP at 4 mg/L significantly reduced the expression levels of the cell cycle regulatory proteins CDK 4, Cyclin D1 and p-Rb. Conclusion: DDP can inhibit the proliferation of A549 cells in combination with O-GSP through a mechanism related to the regulation of cell cycle progression mediated by the Cyclin D1-CDK 4-Rb pathway.

Key words: oligomeric proanthocyanidins from grape seeds, cisplatin, cell proliferation, cell cycle