文献类型：期刊文献

英文题名：Radiosensitization of Osteosarcoma Cells Using the PARP Inhibitor Olaparib Combined with X-rays or Carbon Ions

作者：Dong, Meng[1,2,3,4];Luo, Hongtao[2,5,6];Liu, Ruifeng[2,5,6];Zhang, Jinhua[2,5];Yang, Zhen[2,7];Wang, Dandan[1,2];Wang, Yuhang[1,2];Chen, Junru[1,2];Ou, Yuhong[1,2];Zhang, Qiuning[2,5,6,9];Wang, Xiaohu[1,2,5,6,8]

第一作者：Dong, Meng

通信作者：Wang, XH[1];Zhang, QN[2];Wang, XH[2];Wang, XH[3];Zhang, QN[4]

机构：[1]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[2]Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[3]Chengdu Univ, Clin Med Coll, Chengdu, Peoples R China;[4]Chengdu Univ, Affiliated Hosp, Chengdu, Peoples R China;[5]Univ Chinese Acad Sci, Dept Postgrad, Beijing, Peoples R China;[6]Lanzhou Heavy Ions Hosp, Heavy Ion Therapy Ctr, Lanzhou, Peoples R China;[7]Gansu Univ Chinese Med, Lanzhou, Peoples R China;[8]1 Donggang west Rd, Lanzhou 730000, Peoples R China;[9]1 Yanxia Rd, Lanzhou 730030, Peoples R China

第一机构：Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[2]corresponding author), Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[3]corresponding author), 1 Donggang west Rd, Lanzhou 730000, Peoples R China;[4]corresponding author), 1 Yanxia Rd, Lanzhou 730030, Peoples R China.

年份：2024

卷号：15

期号：3

起止页码：699

外文期刊名：JOURNAL OF CANCER

收录：;Scopus(收录号：2-s2.0-85185550577);WOS:【SCI-EXPANDED(收录号:WOS:001167297900022)】；

基金：We thank Qiuning Zhang for her support during the study. The study was supported by National Key Research and Development Program of China (No. 2022YFC2401505); Science and Technology Plan Project of Chengguan District of Lanzhou (No.2020-2-2-5); Talent innovation and venture project of Lanzhou city (No. 2020-RC-113); Key R & D Program of Science and Technology Department of Gansu Province (No. 20YF8FA116); The authorized project of Lanzhou KejinTaiji Corporation, Ltd (No. BMP-B-02-002); Scientific Technology Research Projects of Gansu Province (No. 22JR5RA121); Gansu Province Project of Science and Technologies (No. 31340612).

语种：英文

外文关键词：osteosarcoma; PARP inhibitor; olaparib; X-rays; carbon ion; radiosensitization

摘要：Objective: Osteosarcomas are derived from bone-forming mesenchymal cells that are insensitive to radiation. This study aimed to investigate the radiosensitization of osteosarcoma cells (U2OS and K7M2) using the PARP inhibitor olaparib combined with X-rays or carbon ions (C-ions). Methods: The effect of olaparib on the proliferation of osteosarcoma cells after irradiation was assessed using CCK-8 and clone formation assays. Cells were treated with olaparib and/or radiation and the effects of olaparib on the cell cycle and apoptosis were analysed by flow cytometry after 48h. Immunofluorescence was used to stain the nuclei, gamma-H2AX, 53BP1, and Rad51 proteins, and the number of gamma-H2AX, 53BP1, and Rad51 foci was observed under a fluorescence microscope. The effect of olaparib combined with radiation on double-stranded DNA breaks in osteosarcoma cells was evaluated. Results: At the same radiation dose, olaparib reduced the proliferation and colony formation ability of irradiated osteosarcoma cells (P < 0.05). Olaparib monotherapy induced minimal apoptotic effects and G2/M phase arrest in osteosarcoma cells and irradiation alone induced moderate apoptosis and G2/M phase arrest. However, radiation combined with olaparib significantly increased the percentage of apoptotic cells and G2/M phase arrest in osteosarcoma cells (P < 0.05). Immunofluorescence experiments showed that compared to the radiation group, the formation of gamma-H2AX and 53BP1 foci was significantly increased in the combined group (P < 0.05). The expression levels of Rad51 foci in the irradiated group were higher than those in the control group (P < 0.05). However, the number of Rad51 foci in the combined group was significantly decreased (P < 0.05). Conclusion: The PARP inhibitor olaparib combined with irradiation (X-rays or C-ions) enhanced the radiosensitivity of osteosarcoma cell lines (U2OS and K7M2). Our findings provide a potential theoretical basis for the clinical application of olaparib in overcoming radiation resistance in osteosarcoma.