中国临床药理学与治疗学
中國臨床藥理學與治療學
중국림상약이학여치료학
CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2007年
8期
869-876
,共8页
颜冬梅%屠凌岚%彭小英%李文钧%沈正荣
顏鼕梅%屠凌嵐%彭小英%李文鈞%瀋正榮
안동매%도릉람%팽소영%리문균%침정영
卵巢肿瘤%赛特铂%顺铂%凋亡%天冬酰胺特异酶切的半胱氨酸蛋白酶
卵巢腫瘤%賽特鉑%順鉑%凋亡%天鼕酰胺特異酶切的半胱氨痠蛋白酶
란소종류%새특박%순박%조망%천동선알특이매절적반광안산단백매
ovarian carcinoma%satraplatin%cisplatin%apoptosis%caspase
目的:观察赛特铂对人卵巢癌细胞A2780的凋亡诱导作用及对细胞周期的影响.方法:MTT法观察药物对细胞增殖的抑制作用,碘化丙锭染色分析细胞周期变化,电镜和荧光显微镜观察细胞形态学变化,多参数流式细胞术及TUNEL法检测细胞凋亡率,并测定caspase-3的活性变化及caspase抑制剂对细胞存活率的影响.结果:赛特铂可抑制A2780细胞的增殖并诱导凋亡,具有明显的剂量依赖性,作用与顺铂相当.赛特铂主要导致A2780细胞S期细胞明显增加,G2/M期细胞少许增加.经赛特铂作用后漂浮细胞呈现典型凋亡细胞形态学改变.caspase-3活性随着细胞凋亡率增加而增加,caspase抑制剂不完全抑制细胞死亡.结论:赛特铂影响A2780细胞周期分布,可体外诱导A2780细胞凋亡.caspase依赖性和caspase非依赖性途径参与了其凋亡过程,其中caspase依赖性途径又包括caspase-3依赖性和非caspase-3依赖性途径.
目的:觀察賽特鉑對人卵巢癌細胞A2780的凋亡誘導作用及對細胞週期的影響.方法:MTT法觀察藥物對細胞增殖的抑製作用,碘化丙錠染色分析細胞週期變化,電鏡和熒光顯微鏡觀察細胞形態學變化,多參數流式細胞術及TUNEL法檢測細胞凋亡率,併測定caspase-3的活性變化及caspase抑製劑對細胞存活率的影響.結果:賽特鉑可抑製A2780細胞的增殖併誘導凋亡,具有明顯的劑量依賴性,作用與順鉑相噹.賽特鉑主要導緻A2780細胞S期細胞明顯增加,G2/M期細胞少許增加.經賽特鉑作用後漂浮細胞呈現典型凋亡細胞形態學改變.caspase-3活性隨著細胞凋亡率增加而增加,caspase抑製劑不完全抑製細胞死亡.結論:賽特鉑影響A2780細胞週期分佈,可體外誘導A2780細胞凋亡.caspase依賴性和caspase非依賴性途徑參與瞭其凋亡過程,其中caspase依賴性途徑又包括caspase-3依賴性和非caspase-3依賴性途徑.
목적:관찰새특박대인란소암세포A2780적조망유도작용급대세포주기적영향.방법:MTT법관찰약물대세포증식적억제작용,전화병정염색분석세포주기변화,전경화형광현미경관찰세포형태학변화,다삼수류식세포술급TUNEL법검측세포조망솔,병측정caspase-3적활성변화급caspase억제제대세포존활솔적영향.결과:새특박가억제A2780세포적증식병유도조망,구유명현적제량의뢰성,작용여순박상당.새특박주요도치A2780세포S기세포명현증가,G2/M기세포소허증가.경새특박작용후표부세포정현전형조망세포형태학개변.caspase-3활성수착세포조망솔증가이증가,caspase억제제불완전억제세포사망.결론:새특박영향A2780세포주기분포,가체외유도A2780세포조망.caspase의뢰성화caspase비의뢰성도경삼여료기조망과정,기중caspase의뢰성도경우포괄caspase-3의뢰성화비caspase-3의뢰성도경.
AIM: To observe the growthinhibiting cell cycle-modifying and apoptosis-inducing effects of satraplatin on human ovarian carcinoma cell line A2780, and to explore its possible mechanism. METHODS: The effect of satraplatin on A2780 cells proliferation was determined using MTT, and the change in cell cycle was analyzed using PI staining. Morphologic change was visualized by fluorescence and electron microscopy. AnnexinV-FITC/PI staining multiparameter flow cytometry and immuno- histochemical TUNEL assay were used to detect apoptotic cells. The activity of caspase-3 and the effect of pan-caspase inhibitor on cell viability were measured as well. RESULTS: The growthinhibiting and apoptosis-inducing effects of satraplatin were dose-dependent and similar to those of cisplatin. Satraplatin mainly caused A2780 cell accumulation in S phase accompanied by minor accumulation in G2/M phase. Cells treated with satraplatin exhibited typical morphology of apoptosis. Satraplatin-induced increase in caspase-3 activity of A2780 cells was concentration-dependent. The viability of A2780 cells was affected by pan-caspase inhibitor z-VAD-fmk in a dose-dependent manner under certain concentration of z-VAD-fmk. CONCLUSION: Satraplatin-induced apoptosis in A2780 in vitro was observed. Caspase-dependent and independent pathways were involved in apoptosis induced by satraplatin, and the latter included caspase-3 dependent and non-caspase-3 dependent pathways.