Effect of apatinib combined with fluzoparib on proliferation ability of human ovarian cancer cisplatin-resistant cells / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the effect of apatinib and fluzoparib on the proliferation ability of cisplatin-resistant human ovarian cancer cells.Methods:Human ovarian cancer cells SKOV3 and cisplatin-resistant SKOV3/DDP cells of human ovarian cancer were treated with different concentrations of 1, 2, 4, 8, 16, 32, 64,128 μg/ml cisplatin at different times; CCK-8 method was used to detect the proliferation rate and half-inhibitory concentration ( IC50) of SKOV3 and SKOV3/DDP cells, and the drug-resistance fold of SKOV3/DDP cell was also calculated. SKOV3/DDP cells were treated with different concentrations of apatinib (4, 8, 16, 32, 64 μmol/L) and fluzoparib (148.15, 222.22, 333.33, 500.00, 750.00 μmol/L) for 24 h, 48 h and 72 h, respectively; the cell proliferation rate was determined by using CCK-8 method and IC50 was calculated. SKOV3/DDP cells were divided into the blank control group (cells untreated with drugs), cisplatin group, cisplatin + apatinib group, cisplatin + fluzoparib group, cisplatin + fluzoparib + apatinib group, and drug intervention was given in each group; the inhibition rate of cells in each group was detected by using CCK8 method. Results:The proliferation rate of SKOV3 cells treated with the same concentration of cisplatin for the same time was lower than that of SKOV3/DDP cells, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 4, 8, 16, 32, 64 μmol/L apatinib was 742.1μmol/L at 24 h, 156.8 μmol/L at 48 h, and 77.5 μmol/L at 72 h. Compared with the control group, the proliferation rate of SKOV3/DDP cells treated with apatinib at an effective concentration greater than 32 μmol/L was significantly decreased, and the differences were statistically significant (all P < 0.05). The IC50 of SKOV3/DDP cells treated with 148.15, 222.22, 333.33, 500.00, 750.00 μmol/L fluzoparib was 878.5 μmol/L at 24 h, 406.7 μmol/L at 48 h, and 283.3μmol/L at 72 h. When the effective concentration of fluzoparib was more than 333.33 μmol/L for 24 h, the proliferation rate of SKOV3/DDP cells was lower than that of the control group, and the differences were statistically significant (all P < 0.05). Compared with the control group, the proliferation rate of SKOV3/DDP cells was decreased when the effective concentration was more than 148.15 μmol/L at 48 h and 72 h, and the differences were statistically significant (all P < 0.05). The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib group was lower than that of 5 μg/ml cisplatin group [(40.4±1.4)% vs. (62.7±1.4)%, t = 20.22, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(5.2±0.4)% vs. (62.7±1.4)%, t = 52.04, P < 0.001]. The cell proliferation rate of 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group was lower than that of 5 μg/ml cisplatin group [(0.3±0.8)% vs. (62.7±1.4)%, t = 53.98, P < 0.001]. The 5 μg/ml cisplatin + 64 μmol/L apatinib + 290 μmol/L fluzoparib group had the lowest proliferation rate of SKOV3/DDP cells, which was lower than that of 5μg/ml cisplatin + 64 μmol/L apatinib group and 5 μg/ml cisplatin + 290 μmol/L fluzoparib group (all P < 0.001). Conclusions:Apatinib and fluzoparib can enhance the sensitivity of human ovarian cancer cisplatin-resistant cells SKOV3/DDP to cisplatin, and the combination of drugs can produce the stronger inhibitory effects and reverse cisplatin resistance of ovarian cancer.