中文摘要：

目的探讨F10基因过表达对肺癌A549细胞裸鼠成瘤的影响及其机制。方法取SPF级裸鼠（4~5周龄）18只,随机均分为A549-WT组、Mock-A549组和F10＋A549组（n=6）,依次接种野生A549细胞（A549-WT）、转染了空载体的对照细胞株（Mock-A549）和已构建的过表达F10基因的A549细胞（F10＋A549）5×106个于颈背部皮下。接种后每3～4d称体重并观察,记录肿瘤发生时间,绘制在体肿瘤生长曲线,计算各组裸鼠的成瘤率。各组裸鼠于接种5周后处死,进行大体观察后取瘤组织块制备石蜡切片,HE染色后行病理组织学观察,并采用免疫组化法检测Caspase-3、Bax和Bcl-2在瘤组织中的表达。结果 A549-WT组、Mock-A549组和F10＋A549组裸鼠的成瘤时间分别为12.0±1.4、11.7±1.0、8.5±1.4d,组间比较差异有统计学意义（F=13.523,P=0.000）,A549-WT组和Mock-A549组裸鼠成瘤时间长于F10＋A549组（P〈0.05）,而前两组比较差异无统计学意义（P=0.660）。大体观察可见,F10＋A549组成瘤体积较A549-WT和Mock-A549组明显增大。F10＋A549组肿瘤的在体生长速度较A549-WT和Mock-A549组增快,差异有统计学意义（P〈0.05）,而后两组间比较差异无统计学意义（P〉0.05）。肿瘤组织HE切片显示,A549-WT和Mock-A549组成瘤组织中存在较多坏死细胞,HE染色表现为均质红染、无定形物质结构,而F10＋A549组成瘤组织边缘细胞坏死较少,细胞增生明显,且肿瘤组织局部可见微血管生成。免疫组化检测显示,Bcl-2蛋白在A549-WT和Mock-A549两组瘤组织中几乎无表达,而在F10＋A549组瘤组织中表达较多,阳性细胞呈弥漫性分布。Bax和Caspase-3蛋白在A549-WT和Mock-A549两组瘤组织中的表达均较强,尤以A549-WT组为显著,但在F10＋A549组瘤组织中表达均很弱。结论 F10基因可通过下调Caspase-3和Bax表达、上调Bcl-2表达而增强肺癌A549细胞株在裸鼠体内的致瘤性。

英文摘要：

Objective TTo explore the effects and mechanism of gene F10 over-expression on the tumorigenicity of A549 cells in nude mice.Methods Eighteen SPF nude mice（4-5weeks of age） were randomly equally divided into the three groups： A549-WT（vaccination with wild-type strain A549）,Mock-A549（vaccination with controlled cells Mock-A549 transfected by blank vectors） and F10＋A549（vaccination with F10＋A549 cells which overexpressed F10 gene） according to their vaccination and then revaccinated into the subcutaneous tissue of the back with cell suspension（0.1ml with 5×106 cells in each mouse）.After vaccination,the mice were observed and weighed once every 3-4 days,then the tumor formation time was recorded,the tumor growth curve drawn and tumor formation rate calculated.The mice were sacrificed and the subcutaneous tumor tissues were paraffin embedded and sectioned,and stained with HE for histopathological examination 5 weeks after the vaccination.Meanwhile,the expressions of Caspase-3,Bax and Bcl-2 in the tumor tissue were detected by immunohistochemistry.Results The tumor formation time was significantly different（F=13.523,P=0.000） between the groups of A549-WT（12.0±1.4d）,Mock-A549（11.7±1.0d） and F10＋A549（8.5±1.4d）,and it was longer in the groups A549-WT and Mock-A549 than that in F10＋A549 group（P〈0.05）,while there was no significant difference between A549-WT and Mock-A549 groups（P=0.660）.General observation of subcutaneous tumor tissues revealed that the tumor volume was increased more significantly in the F10＋A549 group compared with that of the groups A549-WT and Mock-A549.The growth rate of subcutaneous tumor in the F10＋A549 group was increased more significantly compared with groups A549-WT and Mock-A549（P〈0.05）,while there was no significant difference between A549-WT and Mock-A549（P〈0.05）.Pathological examination revealed that the tumor tissues in the groups A549-WT and Mock-A549 harbored more necrotic cells,with structure of homogeneously re