DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment
"Purpose: 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 exp...
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| Format: | Article |
| Language: | English |
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Korean Urological Association
2025-01-01
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| Series: | Investigative and Clinical Urology |
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| Online Access: | https://www.icurology.org/pdf/10.4111/icu.20240263 |
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| _version_ | 1841553382837321728 |
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| author | Jeong Min Lee Won Hyeok Lee Seung Hyeon Cho Jeong Woo Park Hyuk Nam Kwon Ji Hye Kim Sang Hun Lee Ji Hyung Yoon Sungchan Park Seong Cheol Kim |
| author_facet | Jeong Min Lee Won Hyeok Lee Seung Hyeon Cho Jeong Woo Park Hyuk Nam Kwon Ji Hye Kim Sang Hun Lee Ji Hyung Yoon Sungchan Park Seong Cheol Kim |
| author_sort | Jeong Min Lee |
| collection | DOAJ |
| description | "Purpose: 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.
Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay.
Results: 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 medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; 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, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells.
Conclusions: 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."
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| format | Article |
| id | doaj-art-6c72f1faa4ff476b918fa5e12003287a |
| institution | Kabale University |
| issn | 2466-0493 2466-054X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Korean Urological Association |
| record_format | Article |
| series | Investigative and Clinical Urology |
| spelling | doaj-art-6c72f1faa4ff476b918fa5e12003287a2025-01-09T09:19:28ZengKorean Urological AssociationInvestigative and Clinical Urology2466-04932466-054X2025-01-01661566610.4111/icu.20240263DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatmentJeong Min Lee0https://orcid.org/0000-0001-7563-3089Won Hyeok Lee1https://orcid.org/0000-0002-3845-9314Seung Hyeon Cho2https://orcid.org/0009-0009-2701-5281Jeong Woo Park3https://orcid.org/0000-0002-3355-6908 Hyuk Nam Kwon4https://orcid.org/0000-0003-4096-4712 Ji Hye Kim5https://orcid.org/0000-0001-7160-8601Sang Hun Lee6https://orcid.org/0000-0002-6907-8143Ji Hyung Yoon7https://orcid.org/0000-0001-7307-4359Sungchan Park8https://orcid.org/0000-0002-2337-983XSeong Cheol Kim9https://orcid.org/0000-0003-0228-0037School of Biological Sciences, University of Ulsan, Ulsan, Korea.School of Biological Sciences, University of Ulsan, Ulsan, Korea.School of Biological Sciences, University of Ulsan, Ulsan, Korea.School of Biological Sciences, University of Ulsan, Ulsan, Korea.School of Biological Sciences, University of Ulsan, Ulsan, Korea.Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.Basic-Clinic Convergence Research Institute, University of Ulsan, Ulsan, Korea.Basic-Clinic Convergence Research Institute, University of Ulsan, Ulsan, Korea.Basic-Clinic Convergence Research Institute, University of Ulsan, Ulsan, Korea.Basic-Clinic Convergence Research Institute, University of Ulsan, Ulsan, Korea."Purpose: 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. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: 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 medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; 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, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions: 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." https://www.icurology.org/pdf/10.4111/icu.20240263docetaxelparp inhibitorprostate cancer |
| spellingShingle | Jeong Min Lee Won Hyeok Lee Seung Hyeon Cho Jeong Woo Park Hyuk Nam Kwon Ji Hye Kim Sang Hun Lee Ji Hyung Yoon Sungchan Park Seong Cheol Kim DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment Investigative and Clinical Urology docetaxel parp inhibitor prostate cancer |
| title | DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment |
| title_full | DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment |
| title_fullStr | DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment |
| title_full_unstemmed | DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment |
| title_short | DRG2 levels in prostate cancer cell lines predict response to PARP inhibitor during docetaxel treatment |
| title_sort | drg2 levels in prostate cancer cell lines predict response to parp inhibitor during docetaxel treatment |
| topic | docetaxel parp inhibitor prostate cancer |
| url | https://www.icurology.org/pdf/10.4111/icu.20240263 |
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