Imatinib mesylate inhibits androgen-independent PC-3 cell viability, proliferation, migration, and tumor growth by targeting platelet-derived growth factor receptor-α.
Life Sci
; 288: 120171, 2022 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-34822800
ABSTRACT
AIM:
The abnormal expression of oncogenic tyrosine kinase receptors such as platelet-derived growth factor receptors (PDGFRs) has been reported in cancer progression. However, the role of PDGFRs in the human androgen-independent prostate cancer PC-3 cell line is not well understood. Thus, this study examined the role of PDGFRs in androgen-independent PC-3 cells. MAINMETHODS:
PDGFR mRNA and protein expression was determined by quantitative real-time PCR and western blotting, respectively. The effects of the tyrosine kinase inhibitor imatinib (imatinib mesylate) and small interfering RNAs (siRNAs) were determined by a Cell Counting Kit-8 assay, bromodeoxyuridine assay, and Transwell migration assay. The in vivo effect of imatinib was analyzed using a tumor formation assay in nude mice. KEYFINDINGS:
PDGFRα was upregulated in androgen-independent PC-3 cells compared with normal prostate epithelial cells. PDGF-BB induced the phosphorylation of PDGFRα and downstream signaling molecules, including Akt, in a dose-dependent manner. Imatinib reduced the phosphorylation of the PDGFRα/Akt axis. Imatinib also suppressed the viability, proliferation, migration, and tumor growth of PC-3 cells. PDGFRα knockdown by siRNA decreased the viability and migration of PC-3 cells.SIGNIFICANCE:
These results demonstrated the distinct contribution of PDGFRα signaling to the proliferation and migration of PC-3 cells and suggested the potential for PDGFRα as a therapeutic target for metastatic and androgen-independent prostate cancer.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Prostatic Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Cell Movement
/
Receptor, Platelet-Derived Growth Factor alpha
/
RNA, Small Interfering
/
Cell Proliferation
/
Imatinib Mesylate
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Year:
2022
Type:
Article