FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway.

Suocheng Wei,Tuanjie Che,Luju Lai,Zhuandi Gong,Haoqin Liang,Xiaoyun Shen,Yingying Deng

doi:10.18632/oncotarget.25139

Abstract

The present study aimed to investigate FSHreceptor binding inhibitor (FRBI) effects on relative factors (K-Ras, c-Myc and Vascular endothelial growth factor (VEGF)) to ovarian cancer, and expression levels of FSH receptor (FSHR) mRNAs and proteins in the cumulus-oocyte complex (COCs), to determine changes of protein kinase A (PKA) in sheep granulosa cells, further to elucidate signaling pathway of FRBI action. COCs were cultured in vitro for 24h under supplementation of varying concentrations of FRBI (0, 10, 20, 30 and 40μg/mL) or FSH (10IU/mL). Concentrations of K-Ras, c-Myc, VEGF, cAMP and FSH were detected in IVM media fluids, respectively. The results showed that the concentrations of c-Myc, K-Ras and FSH of FRBI groups were gradually reduced with the increase of FRBI doses. VEGF level of the FRBI-4 group was significantly greater than control group (CG). Expression levels FSHR mRNA and protein and PKA of FRBI-3 and FRBI-4 groups were less than that of CG or FSH group (P<0.05 or P<0.01). Inositol trisphosphate (IP3) concentrations of FRBI-3 and FRBI-4 groups were less than FSH group (P<0.05). FRBI administration doses had significant negative correlations to levels or concentrations of K-Ras, c-Myc, VEGF, FSHR mRNA and protein and PKA protein. K-Ras had significant positive correlations with FSHR mRNA and protein and PKA protein. In conclusion, FRBI could promote the production of VEGF of sheep COCs. Higher doses of FRBI (30 and 40μg/mL) suppressed the production of c-Myc and K-Ras, and declined FSH concentrations in the IVM medium fluid, and decreased the expressions of FSHR at the gene and protein levels, additionally attenuated expression of PKA protein in the granulosa cells.

Highlights

Ovarian cancer is a type of cancer that affects one or both ovaries and glands of the uterus
The present study aimed to investigate FSHreceptor binding inhibitor (FRBI) effects on relative factors (K-Ras, c-Myc and Vascular endothelial growth factor (VEGF)) to ovarian cancer, and expression levels of Follicle stimulating hormone (FSH) receptor (FSHR) mRNAs and proteins in the cumulusoocyte complex (COCs), to determine changes of protein kinase A (PKA) in sheep granulosa cells, further to elucidate signaling pathway of FRBI action
To evaluate the effect of FRBI on the production of K-Ras and c-Myc, ELISA assay was performed to detect the concentrations of K-Ras and c-Myc in In vitro maturation (IVM) medium fluid

Summary

Introduction

Ovarian cancer (oophoroma) is a type of cancer that affects one or both ovaries and glands of the uterus. Epithelial ovarian cancer (EOC) is the most lethal female reproductive organ malignancy. The cumulus and granulosa cells in the follicles support oocyte development. The previous studies reported that the retrieval of cumulus-oocyte complexes www.oncotarget.com (COCs) from small antral follicles has been proposed as an attractive option for preserving female fertility in young cancer patients, when controlled ovarian hyperstimulation is unfeasible or unsuitable [2]. In vitro maturation (IVM) of oocytes was a safe and feasible technique for attempting to preserve female fertility in the emergency [3]. The immature oocytes retrieved during the caesarean section were capable of IVM and could lead to live births after fertilization. The immature oocyte collection in the luteal phase was a rescue option for female fertility preservation [4, 5]

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