Human recombinant fsh induces chemoresistance in human breast cancer cells via hif-1 α activation.

Human recombinant fsh induces chemoresistance in human breast cancer cells via hif-1α activation. Biol Reprod. 2019 Apr 02;: Authors: Bergandi L, Canosa S, Pittatore G, Silvagno F, Doublier S, Gennarelli G, Benedetto C, Revelli A Abstract Breast cancer patients under 40 years of age who are candidate to chemotherapy with alkylating drugs may undergo controlled ovarian stimulation (COS) with human recombinant follicle-stimulating hormone (rhFSH) in order to get fertility preservation by mature oocyte cryostorage. The direct effect(s) of exogenous rhFSH on the chemosensitivity of breast cancer is currently unknown. To clarify this issue, we incubated four different breast cancer cell lines with rhFSH (10 IU/L, 24h) and then we exposed them to doxorubicin (DOX) or cyclophosphamide (CPA). The effect(s) of rhFSH on human breast cancer cells treated with DOX or CPA was measured in terms of 1) cell viability, 2) cytotoxicity, 3) multidrug resistance (MDR) genes and proteins expression and activities, and 4) hypoxia-inducible factor 1-alpha (HIF-1α) activation. Pre-treatment with rhFSH significantly increased the viability of breast cancer cells after treatment with DOX or CPA, and reduced the lactate dehydrogenase leakage and reactive oxygen species (ROS) production. Moreover, after pre-incubation with rhFSH, the MDR proteins (Pgp, MPR1 and BCRP) expression and activity resulted up-regulated and the HIF-1α pathway activated. In addition,...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research