Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63
- PMID: 26108997
- DOI: 10.1007/s13277-015-3642-5
Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63
Abstract
Many chemotherapy drugs exert anticancer effects through causing DNA damage, such as DNA topoisomerase inhibitor and platinum-containing drugs. DNA damage repair is an important mechanism of drug resistance which is responsible for metastasis and recurrence after chemotherapy. DNA-dependent protein kinase (DNA-PK) plays an important role in non-homology end joining (NHEJ) pathway. In this study, we aimed to determine whether DNA-PK catalytic subunit (DNA-PKcs) is expressed in osteosarcoma MG63 cell line and involved in drug resistance induced by DNA repair. We found that DNA-PKcs was expressed in osteosarcoma cell line MG63. The pDNA-PKcs(T2609) was more expressed in cells treated with cisplatin (DDP) and etoposide (VP16). Down-regulation of DNA-PKcs produced higher sensitivity of MG63 cells to DDP or VP16 through increasing apoptosis and causing cell cycle arrest in the G1 phase. Our study supported that DNA-PKcs was involved in drug-induced DNA damage repair and related to chemosensitivity of osteosarcoma MG63 cells.
Keywords: DNA damage repair; DNA-PKcs; Drug resistance; Osteosarcoma.
Similar articles
-
Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells.Int J Biochem Cell Biol. 2014 Aug;53:423-31. doi: 10.1016/j.biocel.2014.06.007. Epub 2014 Jun 19. Int J Biochem Cell Biol. 2014. PMID: 24953561
-
Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT) in DNA repair, apoptosis and necrosis after cisplatin.Mol Cancer. 2011 Jun 16;10:74. doi: 10.1186/1476-4598-10-74. Mol Cancer. 2011. PMID: 21679440 Free PMC article.
-
DNA-dependent protein kinase catalytic subunit inhibitor reverses acquired radioresistance in lung adenocarcinoma by suppressing DNA repair.Mol Med Rep. 2015 Jul;12(1):1328-34. doi: 10.3892/mmr.2015.3505. Epub 2015 Mar 18. Mol Med Rep. 2015. PMID: 25815686
-
DNA-PKcs: A promising therapeutic target in human hepatocellular carcinoma?DNA Repair (Amst). 2016 Nov;47:12-20. doi: 10.1016/j.dnarep.2016.10.004. Epub 2016 Oct 15. DNA Repair (Amst). 2016. PMID: 27789167 Review.
-
Mechanisms of DNA double strand break repair and chromosome aberration formation.Cytogenet Genome Res. 2004;104(1-4):14-20. doi: 10.1159/000077461. Cytogenet Genome Res. 2004. PMID: 15162010 Review.
Cited by
-
The inhibition of MARK2 suppresses cisplatin resistance of osteosarcoma stem cells by regulating DNA damage and repair.J Bone Oncol. 2020 Apr 19;23:100290. doi: 10.1016/j.jbo.2020.100290. eCollection 2020 Aug. J Bone Oncol. 2020. PMID: 32368441 Free PMC article.
-
Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells.Biochem Biophys Res Commun. 2017 Apr 29;486(2):307-313. doi: 10.1016/j.bbrc.2017.03.033. Epub 2017 Mar 12. Biochem Biophys Res Commun. 2017. PMID: 28300555 Free PMC article.
-
Experimental Study of Somatic Variants of Osteosarcoma by Whole-Exome Sequencing.Med Sci Monit. 2020 Mar 20;26:e920826. doi: 10.12659/MSM.920826. Med Sci Monit. 2020. PMID: 32193367 Free PMC article.
-
Origin and Therapies of Osteosarcoma.Cancers (Basel). 2022 Jul 19;14(14):3503. doi: 10.3390/cancers14143503. Cancers (Basel). 2022. PMID: 35884563 Free PMC article. Review.
-
DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.J Cancer. 2017 Jul 22;8(12):2410-2416. doi: 10.7150/jca.20069. eCollection 2017. J Cancer. 2017. PMID: 28819445 Free PMC article.
