Investig Clin Urol.  2021 Jul;62(4):485-495. 10.4111/icu.20200574.

Developmentally regulated GTP-binding protein 2 levels in prostate cancer cell lines impact docetaxel-induced apoptosis

Affiliations
  • 1Department of Urology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 2Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 3Department of Urology, Akfa Medline, Tashkent, Uzbekistan
  • 4Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 5Department of Obstetrics and Gynecology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea

Abstract

Purpose
This study aimed to confirm the association between developmentally regulated GTP-binding protein 2 (DRG2) expression and docetaxel-induced apoptosis and to determine whether prostate cancer responses to docetaxel treatment differ with DRG2 expression.
Materials and Methods
PC3, DU145, and LNCaP prostate cancer cell lines were used. The MTT assay was used to determine cell viability. Western blotting analysis was performed using anti-DRG2 antibodies. Cells were transfected with 50 nmol DRG2 siRNA using an siRNA transfection reagent for DRG2 knockdown. The cell cycle was analyzed by using flow cytometry, and apoptosis was detected by using the Annexin V cell death assay.
Results
DRG2 expression differed in each prostate cancer cell line. Docetaxel reduced DRG2 expression in a dose-dependent manner. Upon DRG2 knockdown in prostate cancer cells, an increase in the sub-G1 phase was observed without a change in the G1 or G2/M phases. When 4 nM docetaxel was administered to DRG2 knockdown prostate cancer cell lines, an increase in the sub-G1 phase was observed without increasing the G2/M phase, which was similar to that in DU145 cells before DRG2 knockdown. In PC3 and DU145 cell lines, DRG2 knockdown increased docetaxel-induced Annexin V (+) apoptosis by 8.7 and 2.7 times, respectively.
Conclusions
In prostate cancer cells, DRG2 regulates G2/M arrest after docetaxel treatment. In prostate cancer cells with DRG2 knockdown, apoptosis increases without G2/M arrest in response to docetaxel treatment. These results show that inhibition of DRG2 expression can be useful to enhance docetaxel-induced apoptosis despite low-dose administration in castration-resistant prostate cancer.

Keyword

Apoptosis; DRG2 protein; Prostate cancer
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