Sida Qin, Boxiang Zhang, ChongwenXu, Shuo Li, Hong Ren

Department of Thoracic Surgery, The First AffiliatedHospital of Xi’an Jiaotong University

Objective:Hyperthermia induces cancer cellapoptosis, but its molecular mechanisms remain unclear. Here, we investigatedthe role of Survivin in hyperthermia induced apoptosis in esophageal cancer. Method:EC109 cells were treated with different temperatures. Cell viability wasdetected by MTT assay, and apoptosis was measured by flow cytometry. Celltransfection, western blotting, and immunoprecipitations were used to measurethe mechanisms of hyperthermia. Survivin expression was detected byimmunohistochemistry in esophageal cancer patients, and its correlations withclinicopathological features and prognosis were analyzed by Kaplan–Meiercurves, log-rank tests, and Cox regression models. Result: Duringtreatment with hyperthermia, EC109 cell viability was inhibited, and necrosiswas increased in a temperature-dependent manner. However, the apoptoticratereached its peak at 43℃℃. The hyperthermia-induced apoptosiswas due to the inhibition of Survivin and the activation of Caspase-3.Subsequently, we discovered that over-expression of Survivin inhibited theactivation of Caspase-3 and hyperthermia-induced apoptosis, but this inhibitionwas reversed in the absence of XIAP. Immunoprecipitations showed that Survivindid not directly bind to Caspase-3, but XIAP interacted with both Survivin andCaspase-3. Finally, we found Survivin was expressed at higher levels inesophageal cancer tissues than in normal tissues, and its high expression wascorrelated with poor prognosis. Conclusion: Hyperthermia decreases theexpression of Survivin, prevents its binding to XIAP, activates Caspase-3activation, and induces apoptosis. Due to its correlation with poor prognosis,Survivin might be an essential target for hyperthermia in the treatment ofesophageal cancer.

KeyWords: Hyperthermia  Survivin esophageal cancer