胆管肿瘤·N3邻甲苯甲酰基氟尿嘧啶·氟脲嘧啶·细胞凋亡·

TFu对肝门部胆管癌细胞系FRH0201增殖和凋亡的影响

http://www.100md.com 《中国普通现代外科进展》 2006年第4期

胆管肿瘤·N3邻甲苯甲酰基氟尿嘧啶·氟脲嘧啶·细胞凋亡·细胞周期,,胆管肿瘤·N3邻甲苯甲酰基氟尿嘧啶·氟脲嘧啶·细胞凋亡·细胞周期,TFu对肝门部胆管癌细胞系FRH0201增殖和凋亡

     【摘要】目的：探讨N3邻甲苯甲酰基氟尿嘧啶(N3toluylFlulorouractil TFu)对FRH0201细胞的生物学效应及其作用机制，为胆管癌临床化疗提供参考。方法：光学显微镜、荧光显微镜观察FRH0201细胞在TFu作用后形态学变化；集落形成实验检测TFu对FRH0201细胞的增殖抑制作用；琼脂糖凝胶电泳检测DNA Ladder观察细胞的凋亡；流式细胞术检测细胞周期及细胞凋亡并与5Fu进行比较；MTT试验比较TFu与5Fu等常用化疗药物对FRH0201细胞抑制率。结果：TFu能体外抑制FRH0201细胞的增殖，其作用在0.016~4mmol/L范围内具有浓度依赖性及时间依赖性，同浓度比较抑制率高于5Fu；流式细胞仪检测可见随作用时间延长，TFu及5Fu组G1细胞期增多，S期细胞减少，细胞增殖被阻滞在G1期；细胞凋亡检测可见，随作用时间延长，TFu及5Fu组较对照组细胞凋亡率增加，同时相TFu组凋亡率高于5Fu组；化疗敏感性比较，TFu抑制FRH0201细胞增殖作用不及阿霉素和顺铂，但明显优于5Fu及泰素，联合用药：阿霉素、顺铂和TFu联合对FRH0201细胞抑制率最高，达79.02%，优于阿霉素、顺铂、5Fu联合。结论：TFu可明显抑制胆管癌细胞株FRH0201细胞的增殖，该抑制作用可能通过阻滞细胞周期并进一步诱导细胞凋亡机制发生，同摩尔浓度TFu较5Fu对FRH0201细胞抑制作用强，TFu可作为胆管癌联合化疗的新药。

    【关键词】胆管肿瘤·N3邻甲苯甲酰基氟尿嘧啶·氟脲嘧啶·细胞凋亡·细胞周期

    The effect of TFu on the apoptosis and proliferation of FRH0201 cholangiocarcinoma cell line

    WANG Zhiqing,WU Xiaopeng

    Department of General Surgery,Qilu Hospital of Shandong University(Jinan 250012,China)

    【ABSTRACT】Objective:To investigate the effect of TFu on FRH0201 cell and to test new drugs for the chemotherapy of cholangiocarcinoma.Methods:Morphological changes were observed by light microscopy and fluorescence microscopy.The effect of TFu on FRH0201 cell was examined by clone formation.Cell cycle and apoptosis were examined by flowcytometric analysis.DNA ladder was used to detect apoptosis.To compare the drug susceptibility of TFu with 5Fu and several other common drugs by MTT colorimetric assay.Results:TFu significantly inhibited the proliferation and clone formation of FRH0201 cell line within concentration of 0.016~4mmol/L.The inhibition ratio was dependent on ascending concentration and time,and that is higher than 5Fu with the same concentration.The morphological character of apoptosis was observed.Flow cytometric analysis indicated that TFu induced a G1 phase arrest and apoptosis more than 5Fu.ADM,DDP and TFu were the sensitive drugs to FRH0201 cel line,and the combination of them can reach the highest inhibition ratio.Conclusion:These results suggests that TFu can more significantly inhibited the proliferation of FRH0201 cell line than 5Fu.The mechanism may be related to the cell cycle arrest in association with apoptosis,which may provide a new approach for treating cholangiocarcinoma. ......

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