Abstract：Objective: To investigate the effect of acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) on the formation of radioresistance induced by hypoxia and explored its potential molecular mechanism. Methods: The expression of ACSS2 and p-mTOR in esophageal squamous cell carcinoma(ESCC) tumor tissues from 65 ESCC patients were detect by immunocytochemistry and immunofluorescence technology.The cells were divided into control group, ACSS2 siRNA group, hypoxia group,hypoxia+ACSS2 siRNA group.The clone formation was used to detect the radiosensitivity of the different groups at various doses(0,2,4,6,8 Gy). After treated with 8 Gy irradiation, the apoptotic rate in different groups was detected by flow cytometry. The cleaved-caspase3/caspase3, Bcl-2 protein level and the expression of mTOR, p-mTOR, p70S6 were detected by Western blotting in different groups. Results: The levels of ACSS2 in ESCC tumor tissues were higher and there was a positive correlation between ACSS2 and p-mTOR(r=0.7070， P<0.01) . The results of cell clone test showed that the survival fraction and the radiosensitivity of the hypoxia group were decreased compared with the control group, and the downregulation of ACSS2 could reverse the trend. After 24 h incubation under hypoxia condition, the expression of Bcl-2 protein was significantly increased and cleaved-caspase 3 was inhibited, leading to apoptosis(P<0.01), compared with the normoxia condition.Under hypoxic conditions, down regulation of ACSS2 could inhibit the activation of mTOR signaling related proteins mTOR, p-mTOR, p70S6. Conclusion: The accumulation of ACSS2 induced the radioresistance by the activation of mTOR signaling.
［Key words］ACSS2; irradiation; esophageal squamous carcinoma; radioresistance; mTOR
2017, Vol. 27 
