大肠瘤-癌序列中细胞凋亡及其相关调控基因表达的生物学意义  

Significance of Apoptosis Status and Apoptosisassociated Antigen Expression in Human Colorectal Adenomacarcinoma Sequence

作　　者：李立[1] 严律南[1] 魏于全[1] 刘占培[1] 王忠[1] 雷松[1] 黄光琦[1] 

机构地区：[1]华西医科大学附属第一医院普外科

出　　处：《华西医科大学学报》1999年第2期185-187,191,共4页Journal of West China University of Medical Sciences

摘　　要：为探讨细胞凋亡状态及其相关调控基因表达水平与人大肠癌演进的关系，作者分别采用ＦＣＭ检测短期原代培养的人大肠粘膜、腺瘤及癌细胞不同时相凋亡频率；ＴＵＮＥＬ技术检测２５例腺瘤和７７例腺癌组织中原位凋亡指数（ＡＩ）；免疫组化ＡＢＣ法检测原位增殖指数（ＫＩ）及ｂｃｌ－２、ｂａｘ、ｗａｆ１及ｐ５３基因表达。结果显示：体外培养癌细胞生长期凋亡频率明显低于粘膜细胞；体内瘤－癌组织中ＡＩ与ＫＩ相平衡；高分化和早期癌中ｂｃｌ－２呈高表达，癌前腺瘤、癌栓及远处转移病例中ＡＩ／ＫＩ增高并与ｂａｘ阳性表达和ｗａｆｌ缺失表达有一定联系，ｐ５３突变与高增殖水平有关。从而提示凋亡易感性改变可能在结直肠肿瘤形成早期起着重要作用；ＡＩ可能是一个反映增殖活性的指标；Ｂｃｌ家族基因与大肠癌细胞自发性凋亡及生物学行为有密切关系。To investigate the effects of apoptosis on colorectal tumorigenesis and its possible biological significance, the apoptotic frequency in primary cultural cell of 9 normal mucosa, 4 adenomas and 9 adenocarcinomas in time period of 2, 12, 24, 48 hour was measured by flow cytometry. The apoptotic cells index(AI) in situ for 15 colorectal normal mucosa, 7 hyperplastic epithelial, 25 adenomas and 77 adenocarcinomas was identified by the terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling technique (TUNEL).Ki67 proliferate index (KI), wafl and p53 genes were immunostained with ABC method. The results showed that culture related apoptotic incidence was obviously decreased in cultural tumor cell when compared with mucosa cell after 2448 hour in vitro. There was a directly positive relationship between the spontaneous apoptosis and Ki67index in vivo. The well differentiated or early stage lesions with intensive bcl2 expression were significantly more likely to have low AI and KI. Both accumulation and wafl depression which mainly related to KI, had no apparent correlation with AI, bcl2/bax expression and clinicopathological features statistically; elevatory bax/bcl2 and pervasive wafl depression led to an increasing AI/KI both in adenoma with atypia and in advanced cancer with distant metastasis or embolus, compartively. The data indicated that the reduction of susceptibility to inductive apoptosis may contribute to the early phase of tumorigenesis, that AI in vivo may reflect proliferative activity, and that bcl family was closely associated with spontaneous apoptosis and biological behavior of human colorectal cancer.

关 键 词：细胞凋亡 大肠肿瘤 调控基因 生物学行为 

分 类 号：R735.340.2[医药卫生—肿瘤]