Hyperthermia induces apoptosis by targeting Survivin in esophageal cancer.
Hyperthermia is considered the fifth pillar of cancer treatment. It induces cancer cell apoptosis, however, its molecular mechanisms remain unclear. In the present study, the role of Survivin in hyperthermia-induced apoptosis in esophageal cancer was investigated. Different temperatures were used to treat EC109 esophageal cancer cells, and their viability was found to be significantly inhibited with a concomitant increase in apoptosis and necrosis. Necrosis increased in a temperature‑dependent manner, whereas peak apoptosis was reached at 43˚C. The hyperthermia-induced apoptosis was due to the inhibition of Survivin and the activation of caspase-3. Subsequently, overexpression of Survivin inhibited the activation of caspase-3 and hyperthermia-induced apoptosis, however, this inhibition was reversed in the absence of XIAP. Immunoprecipitations showed that Survivin did not directly bind to caspase-3, whereas XIAP interacted with Survivin and caspase-3. Immunohistochemistry was performed to detect the expression of Survivin in esophageal cancer patient samples. A higher expression of Survivin in esophageal cancer tissues compared to normal tissues was observed, and a high expression correlated with poor prognosis. The results indicated that hyperthermia decreases the expression of Survivin, prevents its binding to XIAP, activates caspase-3 and induces apoptosis. Due to its correlation with poor prognosis, Survivin may be a target for hyperthermia in the treatment of esophageal cancer.
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Sida
S
Qin
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Chongwen
C
Xu
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Shuo
S
Li
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xifang
X
Wang
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xin
X
Sun
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Peili
P
Wang
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Boxiang
B
Zhang
Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Hong
H
Ren
D000328:Adult; D000368:Aged; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505407:CASP3 protein, human; D053148:Caspase 3