Abstract:

Objective To investigate the antiproliferative effects of folate on ovarian cancer cells. Methods Ovarian cancer cells H0-8910 were cultured in vitro, and cell inhibition rates were detected by MTT assay after treatment of ovarian cancer cells with 0 to 160 nmol/L folate for 48 h. Ovarian cancer cells in folate group were treated with 120 nmol/L (50% inhibiting concentration, IC50) folate for 48 h, cells with routine culture were served as control group, and cells in dimethyl sulfoxide (DMSO) group were treated with DMSO. Real-time PCR and Western blotting were performed to observe the mRNA and protein expression of folate receptor (FR-α), dihydrofolate reductase (DHFR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) in the ovarian cancer cells, and flow cytometry was employed to observe the changes of cell cycles. The effects of folate combined with Cisplatin, Paclitaxol or Epirubicin on ovarian cancer cells were detected by MTT. Results The cell inhibition rates increased with the concentrations of folate, and IC50 was 120 nmol/L. The mRNA and protein expression of FR-α, DHFR and MTHFR was lower than that of control group and DMSO group (P<0.05 or P<0.01). Compared with control group, the cell percentage of G2/M phase in folate group decreased (P<0.05), the cell percentage of S phase increased (P<0.05), and there was no significant change in G0/G1 phase (P>0.05). The inhibition rates on ovarian cancer cells of Cisplatin (40 μmol/L), Paclitaxo (10 μmol/L) and Epirubicin (15 μmol/L) combined with 120 nmol/L folate was significantly higher than that of chemotherapeutics lonely (P<0.05). Conclusion The antiproliferative effects of folate on ovarian cancer cells may be achieved by influencing folate metabolism. Folic acid may increase the cytotoxic effect of chemotherapy drugs on ovarian cancer, and increase the chemosensitivity of ovarian cancer.

Key words: ovarian cancer, folate, metabolism, cell cycle, chemosensitivity