中国药理学与毒理学杂志2016，Vol.30Issue(11)：1182-1191,10.DOI:10.3867/j.issn.1000-3002.2016.11.009
信号传导及转录激活子3通路参与卷烟烟气凝集物诱导永生化人支气管上皮细胞的恶性转化
STAT3 signaling pathway participates in malignant transformation of Immortalized human bronchial epithelial cells induced by cigarette smoke condensate
摘要
Abstract
OBJECTIVE To detect the expression of pSTAT3 protein in lung specimens of squa⁃mous cell carcinoma,squamous dysplasia and normal bronchial epithelial tissues,analyze the rela⁃tionship between its expression and smoking,and to explore the role of STAT3 signaling in the process of lung cancer induced by smoking. METHODS pSTAT3 protein expression was assessed by immunohistochemistry in 288 samples of lung specimens of squamous cell carcinoma,108 samples of squamous dysplasia and 112 samples of normal bronchial epithelial tissues. The relationship between its expression and smoking was analyzed. Immortalized human bronchial epithelial cells induced by CSC were divided to 9 groups. Malignant transformation was assessed by resistance to serum-induced terminal differentiation and anchorage-independence growth. pSTAT3 protein expression was detected by Western blotting. The proliferation and apoptosis of P70 treated with JSI-124 0.25-10μmol·L-1 were explored by MTT assay and flow cytometry,respectively. Survivin expression in P70 treated with JSI-124 was detect⁃ed by reverse transcription PCR and Western blotting,respectively. RESULTS Expression of pSTAT3 protein showed a significant upward trend from normal bronchial epithelial tissues were compared to squamous dysplasia and lung specimens of squamous cell carcinoma. pSTAT3 expression wa closely relate to the smoking exposure of patients. With the increase in transformation generation, the resis⁃tance to serum-induced terminal differentiation and anchorage-independence growth were enhanced, especially after P30. pSTAT3 protein expression in normal untreated control and alcohol-treated control groups had no significant difference. pSTAT3 protein expression in BEP2D induced by CSC was higher than that in the two control groups(P<0.05)and their expression increased gradually with the increase in transformation generation. JSI-124 inhibited proliferation and promoted apoptosis in a concentration-and time-dependent manner. The expression of survivin mRNA and protein in P70 treated with JSI-124 1 μmol · L-1 was significantly higher than that in DMSO group(P<0.05). CONCLUSION STAT3 signaling may participate in the malignant transformation of human bronchial epithelial cells induced by tobacco by inhibiting apoptosis of cells through regulation of survivin.关键词
信号传导及转录激活子3/卷烟烟气凝集物/永生化人支气管上皮细胞Key words
STAT3/cigarette smoke condensate/immortalized human bronchial epithelial cells分类
医药卫生引用本文复制引用
袁娜娜,潘秀颉,杨陟华,顾永清,李伟,陈余清,张佳秀,洪磊,蒋鹏,周继红,王效静,朱茂祥..信号传导及转录激活子3通路参与卷烟烟气凝集物诱导永生化人支气管上皮细胞的恶性转化[J].中国药理学与毒理学杂志,2016,30(11):1182-1191,10.基金项目
国家自然科学基金面上项目（81172213）；安徽省自然科学基金面上项目（1408085MH14）；安徽省重点实验室绩效考核补助项目（1506c085013）；安徽省高校自然科学研究项目重点项目（KJ2016A487）；安徽省科技攻关项目（12010402127）@@@@The project supported by National Natural Science Foundation of China （81172213）；Natural Science Foundation of Anhui Province（1408085MH14）；Key Laboratory Performance Assessment Subsidy Program of Anhui Province（1506c085013）；Key Project of Natural Science Research Project in Higher Education of Anhui （KJ2016A487）；and Key Laboratory Project on Department of Science and Technology of Anhui Province （）
