人子宫内膜癌体外化学药物敏感性的实验研究

目的 利用人子宫内膜癌细胞株(HECCL-1)筛选对人子宫内膜癌敏感的化学药物,并探讨其作用机制。方法 采用四甲基偶氮唑蓝(MTY)法体外药敏实验检测HECCL-1细胞对18种不同浓度的化学药物的敏感性。利用流式细胞仪(FCM)进行细胞周期分析,并检测细胞凋亡率及用药前后多药耐药基因MDR1的表达。结果 MTY法结果显示,部分化学药物可显著抑制HECCL-1细胞的增殖,且呈剂量依赖效应,敏感性药物依次为阿霉素、奥铂、卡铂、顺铂、泰素、表阿霉素、放线菌素D、米托葸醌和氟脲嘧啶。FCM检测结果显示,化学药物作用后G0期、G1期细胞显著减少,S期、G2期、M期细胞显著增加。在血浆峰值浓度(PPC)下,11种化学药物作用于HECCL-1细胞后出现细胞凋亡图像。表阿霉素、氟脲嘧啶、羟基喜树碱、米托葸醌4种药物作用后诱导出MDR1阳性表达。结论 HECCL-1是一种化学药物较敏感的细胞株,多种化学药物能够显著抑制HECCL-1细胞的增殖活性,改变其细胞周期分布;诱导细胞凋亡是化学药物作用于该细胞的重要机制;获得性耐药是继续用药失败的主要原因。

Experimental study of sensitivity to chemotherapeutic agents for human endometrial carcinoma cell line

Objective To screen the sensitive chemotherapeutic agents to human endometrial carcinoma cell line-1 (HECCL-1) and study its mechanism. Methods MTT method was used to examine the relative inhibition ratios(RIRs) of various co n centrations of 18 chemotherapeutic agents to HECCL-1. Cell cycle,apoptosis and expression of MDR1 protein were detected by FCM. Results Nine of the chemother apeutic agents studied obviously inhibited the proliferative activity of HECCL- 1 in a dose-dependent manner. The order of sensitivity was as follows: adriamyci n(ADM),oxaliplatin(L-OHP),carboplatin(CBP),cisplatin(DDP),taxol(TAL),epiru bicin(EPI),mitoxantrone(MIT),dactomycin(ACTD) and 5-fluorouracil(5-Fu) . FCM s howed these agents could significantly reduce the proportion of cells in G 0-G 1 p hase,and increase the proportion of cells in S and G 2-M phase ( P <0.0 5). Cell ap optosis was observed in 11 chemotherapeutic agents at their peak concentration. MDR expression was induced after using EPI,5-Fu,hydroxycamptothecin(HCPT) and MIT. Conclusion HECCL-1 is sensitive to a number of the chemotherapeutic agents studied. Induced apoptosis may be the major mechanism of drug sensitivity,and acquired drug-resistance may be the critical reason against continued administr ation.