Breast cancer patients under 40 years of age who are candidate to chemotherapy with alkylating drugs may undergo controlled ovarian stimulation (COS) with recombinant human 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, 24 h) 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-1 alpha) activation. Pretreatment 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 production. Moreover, after preincubation with rhFSH, the MDR proteins (Pgp, MPR1, and BCRP) expression and activity resulted upregulated and the HIF-1 alpha pathway activated. In addition, the use of a widely used HIF-1 alpha inhibitor, the 3-(5-hydroxymethyl-2 '-furyl)-1-benzylindazole (YC-1), prevented the rhFSH effect on the onset of MDR. Taken together, these observations suggest that a short exposure to rhFSH induces chemoresistance to DOX and CPA in human breast cancer cells via HIF-1 alpha activation.Our findings represent the first evidence of a direct role for the recombinant human follicle stimulating hormone in inducing chemoresistance to doxorubicin and cyclophosphamide in different human breast cancer cells via hypoxia-inducible factor 1-alpha activation.

Human recombinant FSH induces chemoresistance in human breast cancer cells via HIF-1 alpha activation

Bergandi, L
First
;
Canosa, S;Pittatore, G;Silvagno, F;Doublier, S;Gennarelli, G;Benedetto, C;Revelli, A
Last
2019-01-01

Abstract

Breast cancer patients under 40 years of age who are candidate to chemotherapy with alkylating drugs may undergo controlled ovarian stimulation (COS) with recombinant human 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, 24 h) 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-1 alpha) activation. Pretreatment 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 production. Moreover, after preincubation with rhFSH, the MDR proteins (Pgp, MPR1, and BCRP) expression and activity resulted upregulated and the HIF-1 alpha pathway activated. In addition, the use of a widely used HIF-1 alpha inhibitor, the 3-(5-hydroxymethyl-2 '-furyl)-1-benzylindazole (YC-1), prevented the rhFSH effect on the onset of MDR. Taken together, these observations suggest that a short exposure to rhFSH induces chemoresistance to DOX and CPA in human breast cancer cells via HIF-1 alpha activation.Our findings represent the first evidence of a direct role for the recombinant human follicle stimulating hormone in inducing chemoresistance to doxorubicin and cyclophosphamide in different human breast cancer cells via hypoxia-inducible factor 1-alpha activation.
2019
100
6
1521
1535
https://academic.oup.com/biolreprod/advance-article/doi/10.1093/biolre/ioz050/5424732
breast cancer cell lines; chemoresistance; hypoxia-inducible factor 1-alpha; multidrug resistance; recombinant follicle-stimulating hormone
Bergandi, L; Canosa, S; Pittatore, G; Silvagno, F; Doublier, S; Gennarelli, G; Benedetto, C; Revelli, A
File in questo prodotto:
File Dimensione Formato  
HUMAN RECOMBINANT FSH INDUCES CHEMORESISTANCE IN HUMAN.pdf

Open Access dal 03/04/2020

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 838.11 kB
Formato Adobe PDF
838.11 kB Adobe PDF Visualizza/Apri
ioz050.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 3.95 MB
Formato Adobe PDF
3.95 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1698537
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 11
social impact