Identification of triosephosphate isomerase as an anti-drug resistance agent in human gastric cancer cells using functional proteomic analysis
Identification of triosephosphate isomerase as an anti-drug resistance agent in human gastric cancer cells using functional proteomic analysis
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使用功能蛋白质组分析鉴定磷酸三糖异构酶作为人胃癌细胞中的抗耐药剂
DOI：
10.1007/s00432-008-0367-5
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发表时间：
2008-02
影响因子：
3.6
通讯作者：
Wang, Xin
中科院分区：
文献类型：
--
作者：
Lan, Mei;Yang, Jinghua;Zhai, Huihong;Shi, Yongquan;Liu, Zhenxiong;Fan, Daiming;Lu, Yuanyuan;Wang, Xin
目的通过蛋白质组学研究探讨胃癌多药耐药（multidrug resistance，MDR）相关蛋白的表达，阐明胃癌MDR发生的新机制。方法采用双向凝胶电泳技术和PDQuest软件分析比较胃癌细胞株SGC 7901和硫酸长春新碱（vincristine sulfate，VCR）诱导的胃癌耐药细胞株（SGC 7901/VCR）中MDR相关蛋白的差异表达。结果通过基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）分析，成功鉴定出9个差异表达蛋白，其中磷酸丙糖异构酶（TPI）是糖酵解途径中表达下调的蛋白。Western blot分析和半定量RT-PCR证实其在SGC 7901/VCR细胞中的表达降低。构建正义表达载体pcDNA3.1-TPI，转染胃癌细胞SGC 7901/VCR。与对照细胞株相比，TPI-SGC 7901/VCR细胞对阿霉素（ADR）、长春新碱（VCR）、5-氟尿嘧啶（5-FU）和顺铂（cis-dichlorodiamine platinum）的敏感性显著增加，对ADR的蓄积和滞留显著增加。可能参与VCR介导的胃癌MDR。TPI表达上调可部分逆转胃癌细胞SGC 7901/VCR的多药耐药表型，提示TPI可能是一种抗胃癌耐药药物，是开发新型胃癌治疗药物的候选靶点。
AimsProteomic study was used to explore new multidrug resistance (MDR)-related proteins and clarify novel mechanism of MDR in gastric cancer.MethodsTwo-dimensional gel electrophoresis and the PDQuest software analysis were applied to compare the differential expression of MDR-related proteins in gastric cancer SGC7901 cells and drug-resistant SGC7901 cells (SGC7901/VCR) induced by vincristine sulfate (VCR). The differential protein dots were excised and further analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis (MALDI-TOF-MS).ResultsNine differential expression proteins between the two cell lines were successfully identified by MALDI-TOF-MS. Triosephosphate isomerase (TPI), a glycolytic pathway enzyme, was identified as a downregulated protein in SGC7901/VCR cells. Further, Western blot analysis and semiquantitative RT-PCR confirmed its decreased expression in SGC7901/VCR cells. Sense vector pcDNA3.1-TPI was constructed and transfected into SGC7901/VCR. The sensitivity of TPI-SGC7901/VCR cells to adriamycin (ADR), VCR, 5-fluorouracil andcis-dichlorodiamine platinum, as well as the accumulation and retention to ADR, were significantly increased when compared to their control cell lines.ConclusionsThese results provide new MDR-related protein candidates, which are differentially expressed in the MDR cell line and its parental cell line including TPI, which may participate in the VCR-mediated MDR in human gastric cancer. Upregulation of TPI expression could partially reverse multidrug-resistant phenotype of SGC7901/VCR, which suggests that TPI may be an anti-drug resistance agent in gastric cancer and the candidate target to develop novel therapeutics for better treatment of gastric cancer.
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影响因子：
4.1
作者：
Anna E. Salinas;M. Wong
通讯作者：
Anna E. Salinas;M. Wong
影响因子：
6.4
作者：
Freire, Teresa;Berois, Nora;Osinaga, Eduardo
通讯作者：
Osinaga, Eduardo
影响因子：
8
作者：
Roesch-Ely, M.;Nees, M.;Bosch, F. X.
通讯作者：
Bosch, F. X.
影响因子：
7
作者：
G. van den Bemd;J. Krijgsveld;T. Luider;A. V. van Rijswijk;J. Demmers;G. Jenster
通讯作者：
G. van den Bemd;J. Krijgsveld;T. Luider;A. V. van Rijswijk;J. Demmers;G. Jenster
影响因子：
2.1
作者：
Nakahara, H;Otani, T;Kogo, M
通讯作者：
Kogo, M