摘要
背景与目的目前大多数研究者分别研究了正常支气管上皮、癌前病变及肺癌组织(吸烟或不吸烟者)标本FHIT蛋白表达,而没有在肺癌发生发展过程中研究其表达及意义。本研究的目的是在烟草特异性亚硝胺(NNK)诱发人支气管上皮细胞(BEAS2B)恶性转化过程中,探讨FHIT蛋白表达的变化及其意义。方法用500mg/LNNK诱发BEAS2B细胞(对照组)恶性转化为BEAS2BNNK细胞(实验组),并在此过程中用免疫细胞化学方法动态观察FHIT蛋白表达的情况。结果㈠NNK诱发BEAS2B细胞恶性转化模型的建立:①第5代BEAS2BNNK细胞血清抗性显著增强;②第15代BEAS2BNNK细胞具有锚着独立性生长特性(软琼脂克隆形成);③第20代BEAS2BNNK细胞超微结构出现明显异型性;④第25代BEAS2BNNK细胞在裸鼠体内成瘤,病理类型为高分化鳞癌。㈡FHIT蛋白表达:BEAS2B细胞FHIT蛋白表达稳定,在各代之间的差异无统计学意义(P>0.05);第5代BEAS2BNNK细胞FHIT蛋白表达即有所降低,并随传代次数增加而进行性下降,但第25代细胞FHIT蛋白却呈高表达。结论①500mg/LNNK能成功诱发BEAS2B细胞恶性转化,为进一步探讨肺癌尤其是吸烟致肺癌的发生机制提供了理想模型。②FHIT蛋白表达减弱在肺癌发生过程中可能属早期事件,但FHIT蛋白在细胞恶性转化晚期上调表达值得进一步研究。
Background and objective Most studies about FHIT protein expression were performed in normal tracheal epithelium, precancerous lesions and lung cancer tissues respectively, but not in the course of malignant transformation of lung cancer. The aim of this study is to detect the changes of FHIT protein expression during malignant transformation of immortalized human bronchial epithelial cells （BEAS-2B） induced by tobacco-specific nitrosamine （NNK）, and to explore its significance. Methods BEAS-2B cells were induced to malignantly transform （BEAS-2BNNK） by 500 mg/L NNK, and FHIT protein expression was detected in the different passages of BEAS-2BNNK and BEAS-2B cells by SP immunocytochemistry, Results Part 1 ： Model of malignant transformation of BEAS-2B cells induced by NNK was established, ①The serum resistance was significantly increased in the 5th passage of BEAS-2BNNK cells, ② The anchorage independent growth （soft agar colony formation） appeared in the 15th passage of BEAS-2BNNK cells, ③The ultrastructure of the 20th passage of BEAS-2BNNK cells showed obvious heteromorphy characterization, ④The 25th passage of BEAS- 2BNNK cells developed into tumors in nude mice, which were well differentiated squamous cell carcinoma, Part 2： FHIT protein was steadily expressed in the different passages of BEAS-2B cells （P〉0. 05）, FHIT protein expression was obviously decreased from 5th to 15th passage of BEAS-2BNNK cells, but it was unexpectedly overexpressed in the 25th passage. Conclusion ①The model of malignant transformation of BEAS-2B cells induced by NNK （500 rag/L） can be established successfully and may be used for investigation of molecular biological mechanisms of lung cancer, especially for smoking-related cases. ②Decrease of FHIT protein expression might be an early event, however, its overexpression in the late passages should be further studied.
出处
《中国肺癌杂志》
CAS
2006年第2期167-172,共6页
Chinese Journal of Lung Cancer
