倍半萜烯内酯通过非caspase途径诱导人鼻咽癌CNE1细胞凋亡  

PARTHENOLIDE INDUCES APOPTOSIS IN HUMAN NASOPHARYNGEAL CARCINOMA CNE1 CELL LINE VIA NON-CASPASE-ACTIVATION PATHWAY

作　　者：林忠宁[1] 林育纯[1] 杨杏芬[2] 朱伟[3] 余贵英[1] 蔡承铿[1] 魏青[1] 

机构地区：[1]中山大学公共卫生学院预防医学系,广东广州510080 [2]广东省疾病预防控制中心,广东广州510300 [3]广州市疾病预防控制中心,广东广州510080

出　　处：《癌变．畸变．突变》2003年第4期195-198,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(No.30070649);广东省自然科学基金(No.001369);美国中华医学基金会(CMB)资助课题

摘　　要：目的 :探讨半胱天冬酶(caspase)活化途径是否在倍半萜烯内酯(SLs)诱导人鼻咽癌(NPC)细胞凋亡中起作用。方法 :CNE1细胞株给予SLs的活性成分 parthenolide(PN)处理 ,以及与caspase-3和 -9特异性抑制剂联合作用进行caspase途径阻断实验 ,检测细胞内caspase -9和 -3活性 ,观察其与细胞毒性和凋亡指标的关系。 结果 :PN作用后细胞TUNEL阳性率和SubG1细胞亚群增高 ,细胞失贴壁率和LDH漏出率显著增加(P<0.05) ,但caspase-9和 -3活性未见升高。特异性抑制剂作用后caspase活性明显降低(P<0.05) ,而细胞凋亡和毒性指标未见明显改变。 结论 :提示PN诱导CNE1细胞凋亡作用与其细胞毒性效应有关 。Purpose: To study whether sesquiterpene lactones(SLs) have the inducible apoptosis effect on human nasopharyngeal carcinoma (NPC) and it's relation with the mechanism of caspase activation, Methods: NPC cell line (CNE1) was treated with parthenolide(PN),the principal active component of SLs. The apoptotic cell death was indicated by morphological alterations. The inducible apoptosis and cytotoxicity effect were determined by flow cytometry, and the cellular caspase-9 and caspase-3 activity was measured by a spectrofluorometric method. Results: The TUNEL positive cell (%) and the SubG1 (%) of cell cycle distribution in creased in PN treated group. Compared with the negative control, there were significant increases of detached cell ratio (%) and lactate dehydrogenase (LDH) leakage (%). However, after PN treatment, the activities of caspase-9 and -3 were not significantly increased. Combined with caspase inhibitors in blocking experiment, PN decreased the caspase-9 and -3 activity but not the apoptotic and cytotoxic index. Conclusion: It was indicated that PN is able to induce apoptosis of CNE1 cell, which may be correlated with cytotoxicity effects but not with caspase cascade activation.[

关 键 词：鼻咽肿瘤 倍半萜烯内酯 细胞凋亡 半胱天冬酶 

分 类 号：R739.63[医药卫生—肿瘤] R979.1[医药卫生—临床医学]