FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway
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Suocheng Wei1,2,*, Xiaoyun Shen3,4*, Luju Lai1, Haoqin Liang2, Yingying Deng2, Zhuandi Gong5 and Tuanjie Che6
1College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, P. R. China
2Research Center of Animal Cell Engineering and Technology of Gansu Province, Northwest Minzu University, Lanzhou, 730030, P. R. China
3School of Karst Science, Guizhou Normal University, Guiyang, 550001, P. R. China
4School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621010, P. R. China
5Medicine College, Northwest Minzu University, Lanzhou, 730030, P. R. China
6Key Laboratory of Functional Genomic and Molecular Diagnosis of Gansu Province, Lanzhou, 730030, P. R. China
*These authors have contributed equally to this work
Zhuandi Gong, email: firstname.lastname@example.org
Tuanjie Che, email: email@example.com
Keywords: FSH receptor binding inhibitor; ovarian cancer; oocyte; K-Ras; signal pathway
Received: September 25, 2017 Accepted: March 22, 2018 Published: April 27, 2018
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.
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