Yong Cai1, Zhaoying Sheng1, Yun Chen1, Jiying Wang2. 1. Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai, China. 2. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai, China.
Abstract
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. IJCEP
OBJECTIVE: To investigate the influence of SIRT6 mediated regulation of cellular glycometabolism on radiosensitivity of A549non-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. IJCEP
Authors: Shih-Chia Tso; Mingliang Lou; Cheng-Yang Wu; Wen-Jun Gui; Jacinta L Chuang; Lorraine K Morlock; Noelle S Williams; R Max Wynn; Xiangbing Qi; David T Chuang Journal: J Med Chem Date: 2017-01-31 Impact factor: 7.446
Authors: Víctor González-Quintana; Lizbeth Palma-Berré; Alma D Campos-Parra; Eduardo López-Urrutia; Oscar Peralta-Zaragoza; Rafael Vazquez-Romo; Carlos Pérez-Plasencia Journal: Oncol Rep Date: 2015-10-30 Impact factor: 3.906