Targeting DNA-PKcs Increased Anticancer Drug Sensitivity by Suppressing DNA Damage Repair in Osteosarcoma Cell Line MG63

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2015 Jun 26

PMID 26108997

Citations 8

Authors

Xin Li

Jiguang Tian

Qiyu Bo

Ka Li

Hongliang Wang

Ting Liu

Jianmin Li

Affiliations

Soon will be listed here.

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.

Citing Articles

N-Methyladenosine modification mediated by METTL3 promotes DNA-PKcs expression to induce anlotinib resistance in osteosarcoma.

Zhang Y, Shen G, Zhang D, Meng T, Lv Z, Chen L Clin Transl Med. 2025; 15(2):e70228.

PMID: 39924638 PMC: 11807765. DOI: 10.1002/ctm2.70228.

Long non-coding RNA GAS5 promotes cisplatin-chemosensitivity of osteosarcoma cells via microRNA-26b-5p/TP53INP1 axis.

Li G, Yan X J Orthop Surg Res. 2023; 18(1):890.

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Origin and Therapies of Osteosarcoma.

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The inhibition of MARK2 suppresses cisplatin resistance of osteosarcoma stem cells by regulating DNA damage and repair.

Xu L, Sun Z, Wei X, Tan H, Kong P, Li Z J Bone Oncol. 2020; 23:100290.

PMID: 32368441 PMC: 7184251. DOI: 10.1016/j.jbo.2020.100290.

Experimental Study of Somatic Variants of Osteosarcoma by Whole-Exome Sequencing.

Hou J, Liu G, Zhang P, Wang B, Yan Q, Wu P Med Sci Monit. 2020; 26:e920826.

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