Abstract
To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4 Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4 Gy X-ray irradiation. In the range of 25 ~ 400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%, 4.23 ± 0.34%, 12.7 ± 2.57%, 22.6 ± 3.38%, 32.2 ± 3.22%, 38.7 ± 4.09% and 47.8 ± 5.58% and there were significantly differences among groups (P < .05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4 ~ 10 Gy X-ray irradiation (P < 0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4 Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, up-regulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis- inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells.
Highlights
Non-small cell lung cancer (NSCLC), a common type of lung cancer with poor prognosis, is one of the main causes of cancer death all over the world (Jemal et al, 2010)
In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised
non-small cell lung cancer (NSCLC) patients take up 80%~85% of total cases in lung cancer (Mutlu et al, 2013; Oven et al, 2013; Aydiner et al, 2013; Cai et al, 2013; Kaya et al, 2013; Natukula et al, 2013; Unal et al, 2013; Wang et al, 2013) and patients with locally advanced NSCLC who can’t receive surgery were mainly treated with radiotherapy, the effect of which was mainly marked with dose-dependence
Summary
Non-small cell lung cancer (NSCLC), a common type of lung cancer with poor prognosis, is one of the main causes of cancer death all over the world (Jemal et al, 2010). The change of sugar metabolic pathway is the common behavior of tumor cells which lays the foundation of macromolecular synthesis for the growth and proliferation of tumor cells (Vander et al, 2009). Multiple studies have revealed that down-regulated expression of lactic dehydrogenase (LDH) and pyruvate dehydrogenase kinase-1 (PDHK-1) can inhibit the growth and proliferation of the tumor (Bonnet et al, 2007; Fantin, et al, 2006; Le et al, 2010), indicating that the change of tumor cell metabolism is of great significance to tumor cell growth and proliferation, which has become a hot issue of prevention and treatment of the tumor. In this study, the radiosensitization effect of overexpression of SIRT6 on A549 cells of NSCLC are explored and the results are reported as follows
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