Abstract: The aim of this study was to investigate the relationship among radiotherapy sensitivity, glutamine synthetase (GS) and autophagy in human hepatocellular carcinoma cells. After X-ray irradiation, CCK-8 and colony formation assay were used to measure the proliferation of HepG2 cells treated with GS inhibitor (L-methionine sulfonimide, MSO). Real-time fluorescence quantitative PCR and protein immunoblotting assays (Western Blot, WB) were used to detect the effect of MSO on GS expression, and GS activity assay kits were used to detect the efficiency of inhibition of GS activity by MSO. Monodansulfonyl cadaverine (MDC) staining as well as WB assay techniques were used to detect intracellular autophagy to determine the effect of IR and MSO on autophagy. The results indicated that MSO caused an increase in intracellular GS expression, but GS activity was significantly inhibited. In addition, MSO reduced the proliferative capacity of cells after radiotherapy and inhibited radiotherapy-induced autophagy. Results suggested that MSO could enhance the sensitivity of HepG2 cells to radiotherapy by inhibiting GS activity, which was closely related to its regulation of autophagic flow.

Key words: glutamine synthetase, cell proliferation, HepG2 cells, autophagy, radiotherapy