International Journal of Radiation Research

en Mefloquine enhances radiosensitivity of glioma cells through ROS-dependent apoptosis Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">Background: Radiosensitizers enhance the effectiveness of radiation therapy by reducing the radio-resistance of cancer cells. A key advantage of traditional drug repositioning over the development of new drugs is the rapid repurposing of existing medications for new therapeutic applications. Mefloquine, a classical antimalaria drug, has also demonstrated anti-tumor activity through various mechanisms. The goal of this study is to investigate the potential of mefloquine as a radiosensitizer on gliomas. Materials and Methods: Gliomas were pre-treated with mefloquine prior to X-ray irradiation. The radiosensitization of mefloquine on these cells was first estimated using a clonogenic formation assay. To determine the mode of cell death, apoptosis and autophagy were measured in U251 gliomas at different intervals after mefloquine-mediated radiosensitization. Additionally, intracellular levels of reactive oxygen species and calcium ions were measured to explore the molecular mechanism during mefloquine-mediated radiosensitization. Results: Mefloquine was demonstrated to present a notable radiosensitizing effect on gliomas. However, the enhancement of protective autophagy diminished the radiosensitizing effect on the first day following combined treatment with mefloquine and X-rays. From the third day onward, the radiosensitization became more pronounced, attributed to a reduction in protective autophagy and an increase in apoptosis. Further study revealed that the increased apoptosis during mefloquine-mediated radiosensitization was dependent on intracellular reactive oxygen species levels, as the apoptotic response was inhibited by glutathione. Conclusion: Our findings demonstrate that mefloquine can elevate the radiosensitivity of gliomas through reactive oxygen species-dependent apoptosis.</div> Radiation-sensitizing agents, mefloquine, glioma cells, apoptosis, reactive oxygen species. 465 471 http://ijrr.com/browse.php?a_code=A-10-1-1518&slc_lang=en&sid=1 A. Wang 7900319475328460033560 7900319475328460033560 No Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, P.R. China Y. Miao 7900319475328460033561 7900319475328460033561 No Department of Radiation Protection, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, P.R. China A. Guo 7900319475328460033562 7900319475328460033562 No Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P.R. China X. Hu 7900319475328460033563 7900319475328460033563 No Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P.R. China Z. Ding 7900319475328460033564 7900319475328460033564 No Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P.R. China X. Zhang zhangxiaohong@nuaa.edu.cn 7900319475328460033565 7900319475328460033565 Yes Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, P.R. China