FOLR1 increases sensitivity to cisplatin treatment in ovarian cancer cells

Abstract

Abstract Background Whether there is a mechanistic link between FOLR1 and response to cisplatin has not been extensively examined. In this study, we determine the expression of FOLR1 in ovarian cancer and examine if FOLR1 levels influence response to cisplatin. Results (1) FOLR1 protein expression was lowest in normal ovarian tissue, higher in benign ovarian tumors, and highest in malignant tumors (P < 0.01). (2) FOLR1 expression was decreased in platinum drug-resistant ovarian tumors compared to sensitive tumors (P < 0.01). Consistent with this, FOLR1 expression in tumors progressing following cisplatin treatment was lower than levels in tumors in remission (P < 0.01). (3) FOLR1 was successfully overexpressed at both the mRNA and protein levels following transfection in SKOV3 cells. (4) SKOV3 cells with FOLR1 overexpression were the most sensitive to cisplatin treatment (IC50 = 3.60 μg/ml) and exhibited the highest inhibition rates in the presence of the drug (P < 0.05). (5) The rate of apoptosis of SKOV3 cells increased with cisplatin treatment in a dose- and time-dependent manner (P < 0.05). Cisplatin also induced S phase arrest in a concentration-dependent manner (P < 0.05). Apoptosis and S phase proportion were significantly altered by FOLR1 overexpression (P < 0.05). Conclusion FOLR1 may be a useful biomarker for ovarian cancer, and it may be useful as a therapeutic application to improve sensitivity to cisplatin treatment.

Keywords

• Folate binding protein
• Ovarian cancer
• SKOV3 cells
• Cisplatin
• Apoptosis
• Cell cycle