马楠楠, 郭献灵, 王晋, 浦浩, 熊海燕, 宋建瑞, 孙凯, 李蓉, 张柏和, 吴孟超, 卫立辛. 胃癌耐药细胞多药耐药基因表达上调中AP-1作用的研究[J]. 中国肿瘤临床, 2008, 35(10): 582-586.
引用本文: 马楠楠, 郭献灵, 王晋, 浦浩, 熊海燕, 宋建瑞, 孙凯, 李蓉, 张柏和, 吴孟超, 卫立辛. 胃癌耐药细胞多药耐药基因表达上调中AP-1作用的研究[J]. 中国肿瘤临床, 2008, 35(10): 582-586.
MA Nannan, GUO Xianling, WANG Jin, PU Hao, XIONG Haiyan, SONG Jianrui, SUN Kai, LI Rong, ZHANG Baihe, WU Mengchao, WEI Lixin. The Role of AP-1 in the Upregulation of the Multidrug Resistance Gene MDR1 in a Drug-Resistant Gastric Carcinoma Cell Line[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2008, 35(10): 582-586.
Citation: MA Nannan, GUO Xianling, WANG Jin, PU Hao, XIONG Haiyan, SONG Jianrui, SUN Kai, LI Rong, ZHANG Baihe, WU Mengchao, WEI Lixin. The Role of AP-1 in the Upregulation of the Multidrug Resistance Gene MDR1 in a Drug-Resistant Gastric Carcinoma Cell Line[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2008, 35(10): 582-586.

胃癌耐药细胞多药耐药基因表达上调中AP-1作用的研究

The Role of AP-1 in the Upregulation of the Multidrug Resistance Gene MDR1 in a Drug-Resistant Gastric Carcinoma Cell Line

  • 摘要: 目的: 探讨人胃腺癌阿霉素耐药细胞系SGC7901/ADR中多药耐药(multi drug resistance,MDR)产生机制,为胃癌多药耐药机制的研究提供新靶点。 方法: 采用MTT法测定3种常用化疗药物顺铂、表柔比星、5-氟尿嘧啶在人胃癌细胞系SGC7901及其阿霉素耐药细胞系SGC7901/ADR中的作用;应用反转录聚合酶链反应(RT-PCR)技术检测SGC7901和SGC7901/ADR中mdr1、c-Jun的mRNA表达情况;转录因子AP-1分别转染入SGC7901和SGC7901/ADR中,应用双荧光素报告基因检测系统(Dual-Luciferase reporter assay system)检测其活性;Western Blot法检测P-gp、c-Jun在蛋白水平的表达。 结果: SGC7901与SGC7901/ADR在化疗药物顺铂、表柔比星、5-氟尿嘧啶的不同浓度下作用72小时后,发现SGC7901/ADR中细胞的生存率无明显改变,而SGC7901的生存率却有显著的下降趋势;在mRNA水平对mdr1基因进行检测,SGC7901/ADR中的多药耐药基因的表达显著高于SGC7901,而P-gp在蛋白水平的检测中显示SGC7901/ADR相对与SGC7901,表达活性有明显升高;转录因子AP-1的表达分别在SGC7901及SGC7901/ADR中检测到,但SGC7901/ADR中AP-1的活性明显高于SGC7901;AP-1的主要组成成份c-Jun在SGC7901和SGC7901/ADR做mRNA及蛋白水平的检测,结果显示在SGC7901中未发现c-Jun的明显表达,而SGC7901/ADR中c-Jun的表达活性均显著升高。 结论: 在人胃腺癌阿霉素耐药细胞系SGC7901/ADR中有MDR的产生,同时伴多药耐药基因上调;转录因子AP-1的活性表达与胃癌细胞的多药耐药性密切相关,AP-1的表达高低可能是其形成机制之一。

     

    Abstract: Objective: To investigate the role of the multi-drug resistance gene MDR1 in the Doxorubicin-resistant SGC7901/ADR gastric adenocarcinoma cell line. Methods: We used the MTT assay to determine the cell survival rate of SGC7901 human gastric carcinoma cells and Doxorubicin-resistant SGC7901/ADR cells after treatment with three kinds of commonly used chemotherapeutic drugs.Reverse transcription-polymerase chain reaction (RT-PCR) was employed to detect the mRNA level of mdr1 and c-Jun in SGC7901 and SGC7901/ADR cells.Transcription factor AP-1 was transfected into SGC7901 and SGC7901/ADR cells, and the transcription activity was assayed by a dual-luciferase reporter assay.The protein ex-pression of P-gp and c-Jun was detected by Western blot. Results: The survival rate of SGC7901/ADR cells was signifi-cantly higher than that of SGC7901 cells.The mRNA level of mdr1 and c-Jun was significantly higher in SGC7901/ADR cells than in SGC7901 cells.The transcription activity of transcription factor AP-1 was different between the two cell lines.The levels of P-gp and c-Jun were higher in SGC7901/ADR cells. Conclusion: In the SGC7901/ADR cell line,multiple-drug resistance is increased and an upregulation of the MDR1 gene is observed.In gastric cancer, the activity of transcription factor AP-1 is related to the MDR of cancer cells.The expression of AP-1 may be involved in the mecha-nism of Doxorubicin resistance in gastric carcinoma cells.

     

/

返回文章
返回