抗癌抗生素力达霉素诱导人肝癌BEL-7402细胞死亡的特征  

CHARACTERIZATION OF CELL DEATH INDUCED BY ANTICANCER ANTIBIOTIC LIDAMYCIN IN HUMAN HEPATOMA BEL-7402 CELLS

作　　者：何琪杨[1] 梁云燕[2] 王代树[2] 李电东[1] 

机构地区：[1]中国医学科学院,中国协和医科大学医药生物技术研究所,北京100050 [2]北京大学临床肿瘤学院北京肿瘤研究所,北京100034

出　　处：《药学学报》2001年第3期174-178,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金! (30 0 70 878) ;国家重点基础研究发展规划基金! (G2 0 0 0 0 5 70 10 )

摘　　要：目的　研究抗癌抗生素力达霉素 (LDM )诱导人肝癌BEL 740 2细胞死亡的特征。方法　用荧光染料Hoechst 33342和PI联染 ;琼脂糖凝胶电泳检测 ;流式细胞术检测等。结果　LDM 1μmol·L-1处理该细胞后 6h ,可观察到一种有别于典型凋亡的染色质凝集方式 :核膜一直保持完整 ,细胞仍贴壁 ,无凋亡小体形成 ;琼脂糖凝胶电泳检测到DNA梯带。流式细胞术检测到的G1亚峰 ,仅在LDM处理BEL 740 2细胞后 2 4h出现。LDM处理BEL 740 2细胞后 6h ,caspase 3,6的活性分别增高 5 ,4倍。染色质开始凝集的时间比caspase 6活性达到高峰的时间早。结论　力达霉素诱导人肝癌BEL 740 2细胞死亡的特征有别于典型的凋亡 。AIM To study the features of cell death induced by the anticancer antibiotic lidamycin (LDM) in human hepatoma BEL 7402 cells. METHODS Chromatin condensation was observed by co staining with fluorescent dyes, hoechst 33342 and propidium iodide. “G1 sub peak” was detected by flow cytometry and DNA ladder was observed using agarose gel electrophoresis. The caspase 3, 6 activities were measured with kits specific for them. RESULTS Typical apoptotic chromatin condensations appeared when the BEL 7402 cells were treated with the conventional antitumor agent mitomycin C 30 μmol·L -1 for 12 h. However, an abnormal type of chromatin condensation occurred when the cells were treated with LDM 1 μmol·L -1 for 6 h, which was characterized with keeping the completeness of nuclear membrane and not forming apoptotic bodies. The DNA ladder patterns were observed using agarose gel electrophoresis. The “G1 sub peak” occurred only in the cells treated with LDM for 24 h, though chromatin condensation was earlier detected in treatment with LDM for 6 h. The caspase 3, 6 activities were increased about 5 and 4 folds, after the cells were treated with LDM 1 μmol·L -1 for 6 h, as did mitomycin C. The time of initiating chromatin condensation was earlier than that of the high peak activities of caspase 6. CONCLUSION The characterization of cell death induced by lidamycin in the human hepatoma BEL 7402 cells differs from typical apoptosis. The results make it helpful to explain the molecular mechanism of the highly potent cytotoxicities of lidamycin toward tumor cells.

关 键 词：抗癌抗生素 力达霉素 人肝癌细胞 细胞死亡 

分 类 号：R735.7[医药卫生—肿瘤] R979.14[医药卫生—临床医学]