| Objective: To investigate the effect of newly synthesized xanthohumol analogues combined with cisplatin on the chemosensitivity of cervical cancer Hela cells and its mechanism. Methods: Cervical cancer Hela cells and normal MRC-5 cells were treated with xanthohumol analogs at different concentrations (5, 7.5, 15, 20 μmol/L) for 48 h. The MTT assay was used to detect the cell proliferation activity and calculate the half inhibitory concentration (IC50) of xanthohumol analogues on two kinds of cells. MTT assay was used to further observe the effect of xanthohumol analogue with the lowest IC50 combined with cisplatin on the proliferation of Hela and MRC-5 cells. Hela cell cycle and apoptosis were detected by flow cytometry. The expression of apoptosis related proteins in Hela cells was detected by Western blot. Results: Xanthohumol analogues a8, a13, b11 and b12 had certain inhibitory effects on the proliferation of cervical cancer Hela cells, and the IC50 value of a13 was the lowest. In addition, the four xanthohumol analogues had a slight inhibitory effect on normal MRC-5 cells, and the IC50 value of A13 was the largest. Compared with the control group, there were no significant differences in the survival rate of normal MRC-5 cells in cisplatin group, a13 group and cisplatin combined with a13 group (P<0.05), but the survival rate of cervical cancer Hela cells, the percentage of G2/M phase cells and the expression level of Bcl-2 protein in cisplatin group, a13 group and cisplatin combined with a13 group were significantly reduced, while the percentage of G0/G1 phase cells, the cell apoptosis rate and cytochrome c (Cyt-c), B lymphoma-2 (Bcl-2) associated X protein (Bax), activated caspase-3 (Cleaved Caspase-3) and activated caspase-9 (Cleaved Caspase-9) protein expression levels increased significantly, and the change range of the above indexes in cisplatin combined with a13 group was significantly greater than that in cisplatin group and a13 group (P<0.05). Conclusion: The combination of xanthohumol analogue and cisplatin can synergistically inhibit the proliferation of cervical cancer Hela cells and show a good chemosensitization effect. Its mechanism may be related to blocking the process of cell cycle, regulating the expression of apoptosis related proteins and promoting apoptosis. |
