DUAN Rongqing,LI Liucen,TANG Qi, et al. The effect and mechanism of carnosine on glioma cell proliferation under normoxic and hypoxic conditions[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(7): 540-547.
Abstract：Objective: To study the effect of carnosine on the proliferation of glioma cells and to explore its mechanism. Methods: Cell samples were divided into normoxia group (21% O2), normoxia carnosine group, hypoxia group (1% O2), hypoxia carnosine group. Under normal oxygen and hypoxia treatment, U251 and U87 cells were treated with 25 mmol/L and 50 mmol/L carnosine, and the changes of glioma cell proliferation were detected by MTT method. The clonal formation experiment was used to detect the change of clonal formation ability of glioma cells. Annexin V-FITC/PI apoptosis was detected by Annexin V-FITC/PI apoptosis assay kit and flow cytometry. Non-targeted metabolomics was used to analyze the metabolic changes of gliomas; LC-MS method was used to detect the change of methionine content in glioma cells. The Western blot method was used to detect the expression levels of c-Myc and LAT1 proteins. C-Myc and LAT1 mRNA levels were determined by RT-qPCR. Results: After carnosine treatment, carnosine can significantly inhibit the proliferation and clonal formation ability of glioma cells under normal oxygen and hypoxic conditions (P<0.05). Carnosine can promote apoptosis in glioma cells (P<0.05). Carnosine had an effect on the amino acid metabolism of U251 cells, which
reduced the content of lysine, methionine and arginine (P<0.05). After carnosine treatment of U251 cells, both c- Myc and LAT1 expression were downregulated (P<0.05). Conclusion: Under normoxic and hypoxic conditions, carnosine can inhibit the proliferation of glioma cells and induce their apoptosis, which may be achieved byinhibiting the c-Myc/LAT1 axis.
