Follicle-stimulating hormone inhibits cervical cancer via NF-?B pathway.

ABSTRACT: Background:Follicle-stimulating hormone (FSH) has multiple biological functions. It is currently considered that FSH can inhibit cervical cancer, and our aim was to explore the underlying molecular mechanisms. Materials and methods:An in vivo experiment using nude mice injected with HeLa cells was performed. Flow cytometry, western blotting, and real-time quantitative PCR analyses were done. Results:Twenty one days after injection of HeLa cells, the subcutaneous tumor mass was significantly lower (P<0.01) in mice treated with 20 mIU/mL FSH, but did not disappear. In vitro observations indicated that FSH might inhibit cell proliferation and activate cell apoptosis to induce the reduction of HeLa cells. The mRNA and protein levels of Cyclin D1, Cyclin E1, and Caspase 3 changed accordingly as expected in vivo and in vitro. Moreover, FSH inactivated the nuclear factor-kappa B (NF-?B) pathway in subcutaneous tumors; the NF-?B(p65) activity in HeLa cells was significantly decreased using 20 mIU/mL FSH and was increased when FSH was administered along with lipopolysaccharide, accompanied by the same change of cell number. Further, FSH accelerated protein kinase A (PKA) activity, but inactivated glycogen synthase kinase 3 beta (GSK-3?) activity. Specific inhibition of PKA and/or GSK-3? provided in vitro evidence that directly supported the FSH-mediated inhibition of GSK-3? to inactivate NF-?B via the promotion of PKA activity. Conclusion:Our data are the first description of the molecular regulatory mechanisms of FSH-mediated inhibition of the development of cervical cancer by decreasing the cell cycle and activating cell apoptosis via the PKA/GSK-3?/NF-?B pathway.

SUBMITTER: Shi X 

PROVIDER: S-EPMC6241696 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature