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.

• Authors: Xin Li, Jiguang Tian, Qiyu Bo, Ka Li, Hongliang Wang, Ting Liu, Jianmin Li
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 12 Pg. 9365-72 (Dec 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26108997 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nuclear Proteins
• Etoposide
• DNA-Activated Protein Kinase
• PRKDC protein, human
• Cisplatin

Topics

• Cell Line, Tumor
• Cisplatin (administration & dosage)
• DNA Breaks, Double-Stranded (drug effects)
• DNA Damage (drug effects)
• DNA Repair (drug effects, genetics)
• DNA-Activated Protein Kinase (biosynthesis, genetics)
• Drug Resistance, Neoplasm (genetics)
• Etoposide (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasm Recurrence, Local (genetics)
• Nuclear Proteins (biosynthesis, genetics)
• Osteosarcoma (drug therapy, genetics, pathology)