Objective: To investigate the influence of SIRT6 mediated regulation of cellular glycometabolism on radiosensitivity of A549 non-small-cell lung cancer (NSCLC) cells.
Methods: Ad-SIRT6 adenovirus vector overexpressed SIRT6 and was established and divided into a control group, a zero-load group (Ad-null), and an overexpression group (Ad-SIRT6). The virus concentration of the Ad-null group and the Ad-SIRT6 group was 200 pfu/cell. The survival factor (SF) after X-ray irradiation of 0, 2, 4, 6, 8, and 10 Gy in three groups was detected by clone formation and cell cycle and apoptosis after 4 Gy X-ray irradiation for 48 hours in the three groups was detected by flow cytometry. Expression levels of pyruvate kinase (PKM), lactate dehydrogenase (LDHA), and hexokinase (HK) after 4 Gy X-ray irradiation of 48 h were detected by qPCR. The glucose level after consumption of (1×106) cells in the medium was detected by a glucose kit.
Results: Compared with the control group and the Ad-null group, SFs after X-ray irradiation of 4-10 Gy in the Ad-SIRT6 group were decreased (P<0.05). A sensitization enhancement ratio of the Ad-SIRT group/the control group was 1.451. After 4 Gy X-ray irradiation of 48 h, the cell ratio and apoptosis rate in G1 phase were increased in the Ad-SIRT6 group, with statistical significance when compared with the other two groups (P<0.05). Compared with the control group and the Ad-null group, levels of PKM, LDHA, and HK mRNA in Ad-SIRT6 group were decreased (P<0.05) and the remaining glucose in the medium was increased (P<0.05).
Conclusion: Overexpression of SIRT6 can inhibit key-enzyme generation in A549 cells to inhibit glycolysis, enhance the radiosensitivity, and lead to G0/G1 phase block as well as cell apoptosis.
Keywords: SIRT6; glycolysis; non-small-cell lung cancer; radiosensitivity.
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