新辅助化疗诱导结肠癌细胞凋亡及IκBα mRNA的表达  

Apoptosis of Colon Cancer Cells and Expression of IκBα-mRNA Induced by Neo-adjuvant Chemotherapy

作　　者：冯斌 陈子华[1] 王光平[1] 石永忠[1] 

机构地区：[1]中南大学湘雅医院

出　　处：《医学临床研究》2003年第10期752-755,共4页Journal of Clinical Research

基　　金：国家自然科学基金项目资助 (30 0 70 945 )

摘　　要：目的探讨羟基喜树碱 (HCPT)联合 5 氟尿嘧啶 (5 Fu)和甲酰四氢叶酸钙 (CF)新辅助化疗诱导结肠癌细胞凋亡及其可能的分子机制。方法2 0例结肠癌患者术前静脉滴入HCPT 10mg/d ,5 Fu5 0 0mg/d,CF 2 0 0mg/d ,共 5天即一周期。术中取结肠癌组织标本 ,应用DNA琼脂糖凝胶电泳检测细胞凋亡的生化改变 ,比色法检测Caspase 3的活性 ,RT PCR半定量技术检测IκBαmRNA的表达 ,并与同期术中取得的 2 0例术前未化疗患者的结肠癌组织及癌旁正常肠组织作比较。结果①新辅助化疗组结肠癌细胞DNA琼脂糖凝胶电泳出现明显的特征性梯状条带 ,术前未化疗组结肠癌细胞无明显的DNA梯状条带 ;②结肠癌细胞Caspase 3活性新辅助化疗组较术前未化疗组结肠癌细胞及癌旁正常结肠细胞明显增高 (P <0 .0 5 ) ;③新辅助化疗诱导后 ,结肠癌细胞IκBαmRNA的表达明显上调 (P <0 .0 5 )。结论HFCF方案新辅助化疗可能通过上调IκBαmRNA表达、激活Caspase 3活性诱导人体内结肠癌细胞凋亡而起作用。ObjectivesTo investigate the apoptosis of colon cancer cells induced by neoadjuvant chemotherapy (NC) composed of hydroxycamptothein (HCPT) in combination with 5-fluorouracil (5-Fu) and calcium folinate (CF) and explore its possible molecular mechanism.MethodsHCPT l0 mg/d, 5-Fu 500 mg/d and CF 200 mg/d were administered IVoi. to 20 patients with colon cancer for 5 days before operation. The specimens from cancer tissues were obtained during operation.The biochemical changes of apoptotic cells were detected with DNA agar gel electrophoresis and their caspase-3 activities were estimated by colorimetry, respectively; while the expression of IkBa-mRNA was assayed by semiquantitative technique of RT-PCR. By comparison, cancerous tissues and normal colon tissues from paracancerous region were collected in 20 patients with colon cancer who were not subjected to chemotherapy.Results①Distinct characteristic bands of apoptotic DNA ladder could be observed by DNA agar gel electrophoresis in NC group, whereas no obvious bands of DNA ladder appeared in non-chemotherapy group;②The caspase-3 activities in cancer cells of NC group were significantly higher than those in cancer cells and normal tissues from paracancerous region of non-chemotherapy group (P<0.05);③After NC, the expression of IκBa-mRNA was markedly up-regulated in colon cancer tissue(P<0.05).ConclusionHFCF project of NC may activate the caspase-3 activity through up-regulation of IκBa-mRNA expression and thus play an important role in the apoptotic induction of colon cancer cells in vivo.

关 键 词：辅助化疗 结肠癌 细胞凋亡 IΚBΑ mRNA表达 羟基喜树碱 5-氟尿嘧啶 甲酰四氢叶酸钙 

分 类 号：R735.35[医药卫生—肿瘤] R730.53[医药卫生—临床医学]