FOLR1 increases sensitivity to cisplatin treatment in ovarian cancer cells

Ming-Ju Huang,Wei Zhang,Zhi-Jun Yang,Li Li,Qi Wang,Sheng-Bin Liao

doi:10.1186/s13048-018-0387-y

Ming-Ju Huang, Wei Zhang + Show 4 more

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https://doi.org/10.1186/s13048-018-0387-y

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Abstract

BackgroundWhether 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).ConclusionFOLR1 may be a useful biomarker for ovarian cancer, and it may be useful as a therapeutic application to improve sensitivity to cisplatin treatment.

Highlights

Whether there is a mechanistic link between Folate binding protein (FOLR1) and response to cisplatin has not been extensively examined
FOLR1 may be a useful biomarker for ovarian cancer, and it may be useful as a therapeutic application to improve sensitivity to cisplatin treatment
Expression of FOLR1 in cancerous ovarian tissue is correlated with clinicopathologic factors FIOG (International Federation of Gynaecology and Obstetrics) system 2000 is used to determine the stages of malignant ovarian patients

Summary

Introduction

Whether there is a mechanistic link between FOLR1 and response to cisplatin has not been extensively examined. We determine the expression of FOLR1 in ovarian cancer and examine if FOLR1 levels influence response to cisplatin. Ovarian cancer is a serious malignancy, with high mortality and a five-year survival rate of approximately 20% - 30% for the prevailing advanced presentations [1]. Survival in patients with ovarian cancer can be improved with early detection, thorough surgery, and improved sensitivity to cisplatin-based chemotherapy. FOLR1 is a glycosyl phosphatidylinositol connected membrane glycoprotein, consisting of 257 amino acids. The protein is completely exposed to extracellular molecules and anchored at the cell membrane by GPI [2]. Its expression levels are closely related with tumor progression and cell proliferation [3, 4].

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