Periprostatic adipose tissue promotes prostate cancer resistance to docetaxel by paracrine IGF-1 upregulation of TUBB2B beta-tubulin isoform.
Adipose Tissue
/ metabolism
Antineoplastic Agents
/ therapeutic use
Cell Line, Tumor
Docetaxel
/ therapeutic use
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Insulin-Like Growth Factor I
/ genetics
Male
Paracrine Communication
/ physiology
Prostatic Neoplasms
/ drug therapy
Tubulin
/ genetics
Up-Regulation
adipocytes
docetaxel
drug resistance
periprostatic adipose tissue
prostate cancer
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
19
02
2021
received:
11
12
2020
accepted:
05
03
2021
pubmed:
19
3
2021
medline:
30
12
2021
entrez:
18
3
2021
Statut:
ppublish
Résumé
Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL-xL, BCL-2, and TUBB2B. AG1024, a well-known IGF-1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF-1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte-released factors and IGF-1 axis to overcome DCTX resistance in patients with PCa.
Identifiants
pubmed: 33734457
doi: 10.1002/pros.24117
pmc: PMC8251776
doi:
Substances chimiques
Antineoplastic Agents
0
TUBB2B protein, human
0
Tubulin
0
Docetaxel
15H5577CQD
Insulin-Like Growth Factor I
67763-96-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
407-417Informations de copyright
© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.
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