Abstract: Objective To explore the effects of mammalian target of rapamycin(mTOR)pathway on radiotherapy-induced autophagy, to search for the small molecular metabolites related to radiosensitivity and their regulatory pathways. Methods ECA109 cells were divided into three groups: control group, radiotherapy group and radiotherapy plus MHY1485 group. The mTOR, Beclin-1 and LC3-II/I were detected with Western blotting, and cell viability 24h after treatment was determined with CCK8 method. The cell culture medium of radiotherapy group(n=6)and radiotherapy plus MHY1485 group(n=6)were collected and analyzed with liquid chromatography-mass spectrometry(LC-MS). The differences in metabolites between the two groups were analyzed with PLS-DA and OPLS-DA. Results Radiotherapy induced autophagy by inhibiting mTOR pathway, and MHY1485 activated mTOR to antagonize autophagy and inhibited proliferation of tumor cells. Compared with the radiotherapy group, the radiotherapy plus MHY1485 group had upregulated expressions of betaine aldehyde, creatine, stearic acid, ornithine, L-cystine and L-proline(P<0.001), but downregulated expressions of citrulline, niacin, glucose 6-phosphate, L-valine, thymine, betaine, L-arginine, L-leucine, L-tryptophan and pyridoxine(P<0.001). Conclusion Radiotherapy can inhibit mTOR-induced autophagy, which 山 东 大 学 学 报 (医 学 版)58卷1期 -章海容,等. 哺乳动物雷帕霉素靶蛋白通路调控ECA109细胞放疗敏感性的代谢组学 \=-can be resisted by the activation of mTOR, so as to inhibit the proliferation of ECA109 cells and enhance the radiosensitivity. As metabolites in the radiotherapy group are different from those in radiotherapy plus MHY1485 group, metabolites and their pathways related to radiosensitivity can be detected with LC-MS technology.

Key words: Mammalian target of rapamycin, Esophageal cancer, Radiosensitivity, Metabonomics