大肠腺瘤及癌中细胞凋亡和bcl-2、bax基因的表达

Apoptosis and the expression of bcl-2, bax genes in coloretal adenoma and carcinoma

目的：探讨细胞凋亡及其调控基因ｂｃｌ－２和ｂａｘ与大肠癌发生发展之间的关系。方法：采用Ｆｅｕｌｇｅｎ染色、ＴｄＴ酶介导的生物素化ｄＵＴＰ缺口末端标记（ＴＵＮＥＬ）技术和免疫组织化学Ｓ－Ｐ法，分别检测大肠正常粘膜、腺瘤、癌及癌旁非腺瘤性不典型增生中细胞凋亡率和ｂｃｌ－２、ｂａｘ基因的表达。结果：大肠腺瘤及癌细胞凋亡率显著高于正常粘膜（Ｐ＜０．０１）。高分化癌凋亡率显著高于低分化癌（Ｐ＜０．０５）。ｂｃｌ－２在正常粘膜腺窝底部、７８．９％（１５／１９）的腺瘤、７５％（３０／４０）的癌及８９．５％（１７／１９）的癌旁不典型增生中有表达。高分化癌与低分化癌阳性率差异显著（Ｐ＜０．０５）。癌的ｂｃｌ－２表达与凋亡率显著负相关（Ｐ＜０．０５）。ｂｃｌ－２／ｂａｘ与大肠癌细胞凋亡率有关（Ｐ＜０．０５）。结论：大肠癌发生过程中细胞凋亡受到抑制，表现为凋亡的相对不足。ｂｃｌ－２／ｂａｘ是影响细胞凋亡的重要因素。

Purpose To approach the action of apoptosis and its regulating genes bcl 2 and bax during carcinogenesis and the development of colorectal carcinoma. Methods Using Feulgen stain, Terminal deoxynucleotidyl Transferase mediated dUTP biotin Nick End Labeling (TUNEL) and immunohistochemistry S P method, the apoptotic indices (AI) (numbers of apoptotic cells/total number of tumor cells) and the expression of bcl 2, bax genes were examined in normal colonic mucosas, adenomas, carcinomas and non adenoma dysplasias adjacent to carcinoma. Results Few apoptotic cells were found in normal colonic mucosas. The AI of tumor tissues was significantly higher than normal tissues( P< 0 01). More apoptotic cells were noticed in well differentiated carcinomas than poorly differnetiated carcinomas ( P< 0 05). Bcl 2 was expressed restrictly in the lower part of normal crypts, and in 15/19 adenomas, 30/40 carcinomas and 17/19 non adenoma dysplasias adjacent to carcinoma. Significant difference of bcl 2 expression was only found between well differentiated and poorly differentiated carcinomas ( P< 0 05). Bcl 2 expression had a significant negativecorrelation with the AI of carcinoma ( P< 0 05). Tissues with low bcl 2/bax possesed higher AI than tissues with high bcl 2/bax ( P< 0 05). Conclusion Apoptosis is inhibited in the process of colonic carcinogenesis. The inhibition of apoptosis may be relatively insufficient. Bcl 2/bax is an important regulator of apoptosis, and the relative predomination of bax promotes the apoptotic death.