Study On The Killing Effect And Mechanism Of Mefloquine Combined With X-ray On Glioma

Radiotherapy is a commonly used treatment for glioma,but glioma cells have radioresistance to X-ray,resulting in poor radiotherapy effect.Radiotherapy sensitizer increase the effect of radiotherapy.However,there are some shortcomings of radiosensitizers,such as the toxicity of radiosensitizers themselves and the failure to reach the lesion smoothly,which limits the application of radiosensitizers.After irradiation injury,tumor cells need to synthesize a large number of proteins to repair the damage.Studies have shown that mefloquine can inhibit protein synthesis by acting on 80 S ribosome subunits,and induce apoptosis through mitochondrial pathway.At the same time,mefloquine has the advantages of smoothly reaching the lesion and low toxicity.Therefore,based on the above points,the radiosensitization of mefloquine to glioma cells was studied in this paper.In this paper,the radiosensitization effect of mefloquine on U251 and C6 cells was evaluated by cell clone formation assay,and the radiosensitization mechanism of mefloquine on U251 cells was further studied.CCK-8 assay was used to study the survival rate of U251 cells after 1,3 and 6 days of mefloquine combined with X-ray treatment,and to observe the level of apoptosis,autophagy and senescence of U251 cells after 1,3 and 6 days of mefloquine combined with X-ray treatment.Finally,the cell cycle,cytoplasmic calcium ion and cytoplasmic ROS level of U251 cells treated by mefloquine combined with X-ray treatment was detected by flow cytometry.The results showed that mefloquine could significantly reduce the survival fraction of glioma cells irradiated by X-ray.The maximal sensitization enhance ratio of U251 cells was 1.64,and that of C6 cells was 1.51.In the study of death mode,the survival rate of U251 cells on the first day of combined action of mefloquine and X-ray was not significantly decreased,which was related to the increase of protective autophagy level on the first day of U251 cell apoptosis,the increase of apoptosis and the decrease of protective autophagy level on the third day of combined action of mefloquine and X-ray,and the further apoptosis on the sixth day of combined action.However,it did not show senescence;therefore,the sensitization effect of mefloquine radiotherapy was mainly attributed to the apoptosis of U251 cells.The increase of apoptosis of U251 cells induced by mefloquine combined X-ray with is due to the increase of ROS level in the cytoplasm.In this paper,the radiosensitization effect and the mechanism of mefloquine on glioma cells was studied,which provided a theoretical basis for the clinical application of mefloquine radiosensitizer.