Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration.
Clin Cancer Res
; 24(22): 5622-5634, 2018 11 15.
Article
em En
| MEDLINE
| ID: mdl-30012567
ABSTRACT
Purpose:
Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer.ExperimentalDesign:
By using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, in vitro macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer.Results:
Treating TRAMP mice with metformin delays prostate cancer progression from low-grade prostatic intraepithelial neoplasia to high-grade PIN, undifferentiated to well-differentiated, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages. Furthermore, metformin is capable of inhibiting the following processes inflammatory infiltration after androgen deprivation therapy (ADT) induced by surgically castration in mice, bicalutamide treatment in patients, and hormone deprivation in LNCaP cells. Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions:
Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment. Clin Cancer Res; 24(22); 5622-34. ©2018 AACR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Microambiente Tumoral
/
Leucócitos
/
Metformina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article