结肠癌TRAIL耐药细胞株的建立及其耐药机制的初步研究

›› 2006, Vol. 18 ›› Issue (5): 340-343.doi:

结肠癌TRAIL耐药细胞株的建立及其耐药机制的初步研究

陈琳琳;朱玉萍;宋章法;黄学锋;毛伟芳

浙江大学医学院附属邵逸夫医院肛肠外科，浙江杭州 310016

收稿日期:2006-02-23 修回日期:2006-04-20 出版日期:2006-09-30 发布日期:2006-09-30
通讯作者: 毛伟芳

Establishment of TRAIL Drug- Resistant Gene in Colon Cancer Cell Subline and Investigation of Its Resistance Mechanism

CHEN Lin-lin，ZHU Yu-ping，SONG Zhang-fa，HUANG Xue-feng，MAO Wei-fang

Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, Zhejiang,China.

Received:2006-02-23 Revised:2006-04-20 Online:2006-09-30 Published:2006-09-30
Contact: MAO Wei-fang

摘要/Abstract

摘要： 背景与目的：以人结肠癌DLD1细胞株为载体，探讨恶性肿瘤获得性TRAIL基因耐药的可能机制。材料与方法：用重组腺病毒介导的TRAIL基因（Ad/gTRAIL）反复处理人结肠癌DLD1细胞，得到耐药细胞群DLD1-TRAIL/R。通过MTT比色法和蛋白电泳，检测耐药细胞对Ad/gTRAIL杀伤作用的敏感性及其凋亡通路中信号分子的表达情况，分析其获得性耐药的可能机制。结果：DLD1-TRAIL/R细胞对Ad/gTRAIL和重组TRAIL蛋白处理耐药，但对腺病毒介导的Bax基因处理仍然敏感。耐药细胞内 Bcl-XL的表达明显升高， caspase-8的表达显著下降，未见明显的caspase-8活性裂解形式。结论：人结肠癌DLD1细胞株经Ad/gTRAIL反复处理后产生特异性针对TRAIL基因的耐药，其发生机制可能与Bcl-XL表达上调和caspase-8表达下调有关。

关键词: TRAIL, 基因治疗, 耐药

Abstract: BACKGROUND ＆ AIM: To evaluate the mechanisms involved in acquiring the TRAIL drug-resistance gene in human colon cancer DLD1 cell line. MATERIAL AND METHODS: DLD1 cells were repeatedly treated with adenovirus-mediated TRAIL gene(Ad/gTRAIL), and DLD1-TRAIL/R cells resistant to Ad/gTRAIL were obtained. The cell growth was measured by MTT method. The expression of proteins involved in TRAIL-mediated apoptosis pathway was also showed by western blot analysis. Then the possible mechanisms involved in acquiring resistance were analyzed. RESULTS： DLD1-TRAIL/R cells resistant to TRAIL were obtained from TRAIL-sensitive DLD1 parent cells. But they were still sensitive to adenovirus-mediated Bax gene therapy. Further studies demonstrated that expression of Bcl-XL was dramatically increased whereas caspase-8 was significantly decreased in DLD1-TRAIL/R cells. Simultaneously, there was no cleaved caspase-8 found in the DLD1-TRAIL/R cells. CONCLUSION: After repeated treatment, DLD1 cells could acquire the specific resistance to TRAIL gene. The involved mechanisms may involve up-regulation of Bcl-XL and down-regulation of caspase-8.

Key words: TRAIL, gene therapy, resistance

陈琳琳;朱玉萍;宋章法;黄学锋;毛伟芳. 结肠癌TRAIL耐药细胞株的建立及其耐药机制的初步研究[J]. , 2006, 18(5): 340-343.

CHEN Lin-lin，ZHU Yu-ping，SONG Zhang-fa，HUANG Xue-feng，MAO Wei-fang. Establishment of TRAIL Drug- Resistant Gene in Colon Cancer Cell Subline and Investigation of Its Resistance Mechanism[J]. , 2006, 18(5): 340-343.

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