title: 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.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Emergency Department, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Tian
authors.affiliation: Operating room of Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Bo
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Ka
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China. gkljmin@outlook.com.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000096:biosynthesis* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology
chemical_list: D009687:Nuclear Proteins; D005047:Etoposide; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D002945:Cisplatin
keywords: DNA damage repair; DNA-PKcs; Drug resistance; Osteosarcoma