肿瘤坏死因子相关凋亡诱导配体对肝癌耐药细胞株阿霉素化疗敏感性的影响  

Tumor necrosis factor related apoptosis-inducing ligand induces apoptosis and sensitizes resistant hepatic cancer cells to chemotherapy

作　　者：何松青[1] 陈孝平[1] 张万广[1] 王海平[1] 王其[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科中心,武汉430030

出　　处：《中华肝脏病杂志》2004年第8期456-459,共4页Chinese Journal of Hepatology

基　　金：卫生部临床重点学科项目(2001)

摘　　要：目的 研究肿瘤坏死因子相关凋亡诱导配体(TRAIL)联合阿霉素(ADM)处理肝癌耐药细胞株HepG2/ADM对化疗敏感性的影响。 方法 通过培养液中ADM的浓度梯度增加法长期筛选培养,建立肝癌HepG2/ADM耐药细胞株,荧光定量PCR检测多药耐药(MDR)1的表达,TRAIL联合化疗药物ADM处理HePG2/ADM,MTT比色法检测细胞增殖,细胞凋亡采用流式细胞仪和TUNEL法检测观察HepG2/ADM对化疗药物的敏感性变化。 结果 HepG2/ADM细胞是一个明确的多药耐药细胞模型,联合TRAIL(100ng/L)+ADM(0.1 mg/L)后,MTT显示HepG2/ADM细胞的增殖明显抑制,流式细胞术、TUNEL法检测TRAIL联合ADM处理HepG2/ADM 细胞诱导的凋亡,与对照组相比,凋亡指数显著增加。 结论MDRI不参与TRAIL耐受。TRAIL可部分逆转HepG2/ADM对ADM的耐药,增加其对化疗药物的敏感性。联合TRAIL和亚毒剂量化疗药物可望克服肿瘤细胞中存在的化疗耐药和TRAIL耐受。Objective To investigate the effective of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) combination with chemotherapeutic agent inducing apoptosis in resistant hepatic cancer cells. Methods HepG2 cells resistant to Adriamycin (HepG2/ADR) were induced stepwise. The effects of TRAIL in combination with ADM (0.1 mg/L) on promoting apoptosis in HepG2/ADR were analyzed, the proliferation was observed by MTT assay, the apoptosis of cells was also observed by flow cytometry and TUNEL method. Results HepG2/ADR was confirmed resisting to ADM. Treated with TRAIL combination with ADM (0.1 mg/L), it showed significant inhibitory effect on the growth of HepG2/ADM, the percentage of apoptosis was increased as comparison with control at 24 h. Conclusion MDR1 might not take part in resistance to TRAIL-induced apoptosis. TRAIL dramatically augmented the sensitivity to chemotherapeutic agents in HepG2/ADR. Combined TRAIL with chemotherapeutic agents treatment could be a novel and attractive strategy to drug-resistant/ TRAIL-resistant tumor cells.

关 键 词：肿瘤坏死因子相关凋亡诱导配体 肝癌 耐药细胞 阿霉素 化疗敏感性 

分 类 号：R735.7[医药卫生—肿瘤]