DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor

Abstract

Abstract Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Cell viability was determined using a Cell Counting Kit (CCK) assay; anti-DRG2 antibodies were used for western blotting. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. The cell cycle was analyzed using flow cytometry, and apoptosis was detected using the Annexin V cell death assay. The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and wild-type, respectively. In PC3 (DRG2-high, p53 null), docetaxel increased G2/M arrest but no apoptosis was observed; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2-low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2-high), docetaxel increased sub-G1 and G2/M arrest and induced apoptosis, whereas olaparib enhanced apoptosis. Docetaxel and olaparib combination treatment had a slight effect on DRG2-knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Therefore, DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.