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Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63

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Tumor Biology

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-PKcsT2609 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.

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Acknowledgments

This study was funded by the National Natural Science Foundation of China (81172551) and the Shandong Technological Development Project (ZR2011HM037).

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    Authors and Affiliations

    1. Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China

      Xin Li, Ka Li, Hongliang Wang & Jianmin Li

    2. Emergency Department, Qilu Hospital, Shandong University, Shandong, China

      Jiguang Tian

    3. Operating room of Qilu Hospital, Shandong University, Shandong, China

      Qiyu Bo

    4. Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Shandong, China

      Ting Liu

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    1. Xin Li
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    2. Jiguang Tian
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    4. Ka Li
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    5. Hongliang Wang
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    7. Jianmin Li
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    Correspondence to Jianmin Li.

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    Xin Li and Jiguang Tian contributed equally to this work.

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    Li, X., Tian, J., Bo, Q. et al. Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line MG63. Tumor Biol. 36, 9365–9372 (2015). https://doi.org/10.1007/s13277-015-3642-5

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    • DOI: https://doi.org/10.1007/s13277-015-3642-5

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