Sida Qin¹, Boxiang Zhang², Chongwen Xu², Shuo Li², Xifang Wang², Xin Sun², Peili Wang², Hong Ren²

¹Department of Thoracic Surgery, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, ²School of Medicine, First Affiliated Hospital

Objective:Hyperthermia induces cancer cellapoptosis, but its molecular mechanisms remain unclear. Here, we investigated the role of Survivin in hyperthermia induced apoptosis in esophageal cancer. Method: EC109 cells were treated with different temperatures. Cell viability was detected by MTT assay, and apoptosis was measured by flow cytometry. Cell transfection, western blotting, and immunoprecipitations were used to measure the mechanisms of hyperthermia. Survivin expression was detected by immunehisto-

chemistry in esophageal cancer patients, and its correlations with clinicopathological features and prognosis were analyzed by Kaplan–Meier curves, log-rank tests, and Cox regression models. Result: During treatment with hyperthermia, EC109 cell viability was inhibited, and necrosis was increased in a temperature-dependent manner. However, the apoptotic rate reached its peak at 43℃. The hyperthermia-induced apoptosis was due to the inhibition of Survivin and the activation of Caspase-3. Subsequently, we discovered that over-expression of Survivin inhibited the activation of Caspase-3 and hyperthermia-induced apoptosis, but this inhibition was reversed in the absence of XIAP. Immunoprecipitations showed that Survivin did not directly bind to Caspase-3, but XIAP interacted with both Survivin and Caspase-3. Finally, we found Survivin was expressed at higher levels in esophageal cancer tissues than in normal tissues, and its high expression was correlated with poor prognosis. Conclusion:Hyperthermia decreases the expression of Survivin, prevents its binding to XIAP, inhibits Caspase-3 activation, and induces apoptosis. Due to its correlation with poor prognosis, Survivin might be an essential target for hyperthermia in the treatment of esophageal cancer.

Key Words: Hyperthermia  Survivin  esophageal cancer