新辅助化疗诱导大肠癌凋亡caspase-3活性的研究

目的 :对羟基喜树碱 (HCPT)联合 5 氟脲嘧啶 ( 5 Fu)和甲酰四氢乙酸钙 (CF)方案的新辅助化疗进行研究 ,以了解该方案的化疗作用机制。方法 :2 0例大肠癌患者术前静脉滴入HCPT10 0mg/d ,5 Fu 5 0 0mg/d ,CF2 0 0mg/d ,共 5d ,一周期。术中取大肠癌组织标本 ,应用光镜观察凋亡细胞形态学改变 ,比色法检测caspase 3的活性 ,与术前结肠镜下取得的该组癌组织及同期术中取得 14例未化疗患者的正常肠黏膜组织作比较。结果 :①术前应用化疗组在光镜下可见到明显的细胞凋亡改变 ;②术前应用化疗组的caspase 3活性较未化疗及正常肠黏膜组的明显增高 (P <0 .0 5 ) ;③术前化疗诱导后 ,肿瘤细胞caspase 3活性改变与肿瘤的分期及肿瘤分化程度有关。结论 :术前应用HCPT联合 5 Fu和CF方案可诱导大肠癌细胞凋亡 ,caspase 3参与了这一细胞凋亡过程 ,且caspase 3的活性改变与肿瘤分期及分化程度有关。

Effect of the change of caspase-3 activity on the neoadjuvant chemotherapy-induced apoptosis of large-intestinal carcinoma cells

Objectives To study the change of caspase-3 activity on the neoadjuvant chemotherapy-induced apoptosis by hydroxycamptothecin (HCPT) with 5-fluorouracil (5-Fu)/leucovorin(CF) in large-intestinal carcinoma, and to explore its mechanism. Methods HCPT 100mg/d 1-5, 5-Fu 500mg/d 1-5 and CF 200mg/d 1-5 were administered intravenously to 20 pre-operation patients. Samples were obtained during the operation. The changes of apoptotic cells and caspase-3 activity in large-intestinal carcinoma were evaluated with the optical microscopy and the colorimeteric assay respectively and were compared with non-chemotherapy group and normal intestinal tissue group. Results ①The obvious cell apoptotic change could be observed under the optical microscopy in the neo-adjuvant chemotherapy group; ②The level of caspase-3 activity was significantly higher in the neo-adjuvant chemotherapy group than in the non-chemotherapy and normal intestinal tissue group(P<0.05);③The change of caspase-3 activity was closely correlated with the tumor differentiation and Dukes stage ofter the induction of pre-operative chemotherapy. Conclusion HCPT combined with 5-Fu/CF may induce the apoptosis of large-intestinal carcinoma cells and caspase-3 takes part in the apoptotic process. The change of caspase-3 activity was closely correlated with the degree of the tumor differentiation and Dukes stage.