Receptor Binding Inhibitor Suppresses Carcinogenesis of Cervical Cancer by Depressing Levels of FSHR and ERβ in Mice

Author(s):

Zhuandi Gong, Xiaoyun Shen, Juan Yang, Luju Lai and Suocheng Wei*   Pages 1719 - 1727 ( 9 )

Abstract:

<P>Background: FSH Receptor Binding Inhibitor (FRBI) blocked the binding of FSH to FSHR. Our initial study revealed FRBI reduced the maturation rate, enhanced the apoptosis of sheep Cumulus-Oocyte Complex (COCs). Little is known about whether FRBI modulates ER&#946; and FSHR levels in the normal uterine and cancerous tissues. The present study aimed to evaluate the FRBI effects on the expressions of Estrogen Receptor-beta (ER&#946;) and FSH receptor (FSHR) in the uteri. </P><P> Methods: 150 mice were assigned to FRBI+FSH (COM), FSH and control groups (CG). Mice of COM-1, COM-2 and COM-3 groups were simultaneously intramuscularly injected with 500, 750 and 1000 &#181;g FRBI with 10 IU FSH, respectively for five days. Western blotting and qPCR were utilized to determine the expression of ER&#946; and FSHR. </P><P> Results: In comparison with FSH group, uterine lumen and glands of COM groups became narrow. The uterine wall and endometrial epithelium were thinned, and uterine lumen became narrow. Epithelial cells were decreased. Uterine wall thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 6.49%, 14.89% and 15.69% on day 30 as compared with FSH group. Uterine perimetrium thicknesses of COM-1, COM-2 and COM-3 groups were reduced by 16.17%, 17.93% and 19.92% on day 20 in comparison with FSH group. Levels of FSHR mRNAs and proteins of COM-1, COM-2 and COM-3 groups were less than FSH group on days 20 and 30 (P<0.05). ER&#946; protein of COM-3 group was less than FSH group. Serum estradiol (E2) and FSH concentrations of COM-2 and COM-3 were lower than that of FSH group on day 30. </P><P> Conclusion: FRBI could decrease UWT and UPT, also block the uterine development, decline expression levels of ER&#946; and FSHR protein. Additionally, FRBI reduced the secretion of secretion of FSH and E2. Downregulating expression of FSHR and ER&#946; may be a potential treatment regimen for cervical cancer patients.</P>

Keywords:

Uterine cancer, follicle stimulating hormone receptor, FSH receptor binding inhibitor, estrogen receptor, estradiol, mice.

Affiliation:

Hospital of Medicine College, Northwest Minzu University, Lanzhou, 730030, School of Karst Science, Guizhou Normal University, Guiyang, 550001, College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030

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