结肠癌细胞凋亡与增殖的平衡及其与预后的关系  

Cell Balance between Apoptosis and Proliferation in Colon Cancer and Its Correlation with Prognosis

作　　者：陈金明[1,2] 李伟华[1] 王家顿 冯永东[1] 吴剑宏[1] 龚建平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院普外科/肿瘤研究所 [2]浙江大学医学院附属第二医院外科,浙江杭州310009

出　　处：《癌症》2005年第5期554-558,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金(No.39730270);国家杰出青年基金(No.39725027);973肿瘤计划(No.G1998051212);卫生部临床重点学科资助项目(No.20012537)~~

摘　　要：背景与目的:人体正常组织器官中,特定组织中凋亡与增殖细胞维持着动态平衡,一旦凋亡与增殖的平衡被打破,将导致细胞的恶性转化和肿瘤的发生。我们通过研究结肠癌细胞和淋巴细胞演进过程中凋亡与增殖平衡机制的变化,及其与患者生存的关系,探讨结肠癌的发生、发展规律。方法:采用低分子量DNA抽提后荧光染料染色法(Sub G1法)和Ki-67/DNA双参数法,分别定量分析凋亡群体和增殖群体。应用激光共聚焦显微镜对组织细胞的增殖进行形态学观察,Kaplan-M eier法分析生存率。结果:对照组细胞、腺瘤细胞、肿瘤组Dukes蒺A期、B期、C+D期细胞中,凋亡指数/增殖指数(apoptosis index/proliferating index,AI/PI)分别为0.45±0.19、0.30±0.07、0.29±0.11、0.28±0.10和0.26±0.07。对照组的AI/PI大于其余4组(P<0.01)。在结肠癌细胞的大小、类型、分化程度、Dukes蒺分期和淋巴结转移等临床病理特征中,AI/PI总体呈下调的趋势。正常人和肿瘤患者外周血淋巴细胞AI/PI分别为0.49±0.12和0.64±0.11。肿瘤患者淋巴细胞的AI/PI大于对照组(P<0.01)。用激光共聚焦显微镜可观察到结肠对照组、腺瘤和肿瘤组织中Ki-67的表达。根据AI/PI的中位数值0.285,将结肠癌患者分为≥0.285组和<0.285组。经log-rank检验两组患者生存时间无显著性?BACKGROUND & OBJECTIVE: In normal tissues and organs, cell apoptosis and proliferation maintain a homeostasis. Alterations of this physiologic balance may lead to malignant transformation of cells and tumorigenesis. This study was to investigate cell balance (ratio of apoptosis index to proliferation index, AI/PI) in colon cancer and its correlation with prognosis. METHODS: The apoptotic population and the proliferating population of colon cancer cells were quantitatively analyzed by Sub-G1 method and Ki-67/DNA bivariate analysis of flow cytometry. Cell proliferation was observed under confocal microscope. Kaplan-Meier method and log-rank test were used to analyze patients' survival. RESULTS: AI/PI ratio of cells was significantly higher in normal colon tissue than in colon adenoma tissue, Dukes' A colon cancer, Dukes' B colon cancer, and Dukes' C and D colon cancer (0.45±0.19 vs. 0.30±0.07, 0.29±0.11, 0.28±0.10, and 0.26±0.07, respectively, P < 0.01). AI/PI ratio showed a down-regulating trend in variables tested including tumor size, pathologic type, differentiation grade, Dukes' stage, and nodal involvement. AI/PI ratio of peripheral lymphocytes was significantly higher in colon cancer patients than in healthy people (0.64±0.11 vs. 0.49±0.12, P < 0.01). The expression of Ki-67 was observed in normal colon tissue, colon adenoma, and colon cancer under confocal microscope. Survival rate of patients with AI/PI ratio of < 0.285 (using the median value as the cutoff) and ≥ 0.285 wasn' t significantly different (P> 0.05). CONCLUSIONS: Dysregulation (down-regulation or up-regulation) of cell balance between apoptosis and proliferation in colon cancer cells and lymphocytes might play an important role in tumorigenesis and tumor progression. AI/PI ratio can' t be used as a prognostic factor of colon cancer.

关 键 词：结肠肿瘤 凋亡 增殖 预后 流式细胞术 激光共聚焦显微镜 

分 类 号：R735.35[医药卫生—肿瘤]