关键词:  喉肿瘤, Stat3, 低氧, 反义寡核苷酸, 化疗增敏

Abstract: Objective To investigate changes in apoptosis and cell cycle progression in Hep-2 cells after treating them with cisplatin and antisense oligonucleotides targeting the signal transducer and activator of transcription 3（Stat3）. Methods Hep-2 cells were transfected with different concentrations of liposome-encapsulated Stat3 sense or antisense oligonucleotides.The cells were then exposed to different cisplatin doses（0-5 μg/ml） in normoxic and hypoxic environments， and their sensitivity was measured in the MTT survival assay.Cell cycle progression and apoptosis were examined by flow cytometry. Results Apoptosis increased with increasing doses of cisplatin in both hypoxic and normoxic conditions.Rate of apoptosis was similar between cells treated with 1 μg/ml DDP under hypoxic conditions and untreated control cells under normoxic conditions（P>0.05）.However，cells treated with 3 or 5 μg/ml cisplatin under hypoxic conditions showed a lower apoptosis rate than cells under normoxic conditions（P<0.01）.Transfecting cells with Stat3 antisense oligonucleotides decreased Hep-2 survival under hypoxic conditions in a dose-dependent manner（100-400 nmol/L） and led to cell cycle blockade at G₀ /G₁ phase.The rate of apoptosis in cultures treated with Stat3 antisense oligonucleotides and cisplatin together was significantly different from the rates in control cultures and in cultures treated with sense oligonucleotides and cisplatin together， antisense nucleotides on their own，or cisplatin on its own（P<0.01）. Conclusions Treating Hep-2 cells with Stat3 antisense oligonucleotides and cisplatin together can induce apoptosis under hypoxic conditions and increase sensitivity to chemotherapy.Gene therapy involving RNA interference targeting Stat3 may be a new approach to adjuvant chemotherapy for laryngeal carcinoma.

Key words: Laryngeal neoplasms, Stat3, Hypoxia, Antisense oligonucleotide, Chemotherapy sensitization