黄声凯,王 佳,李 燕.组织蛋白酶D增强胃癌细胞对顺铂敏感性的研究[J].中国肿瘤,2018,27(3):218-222.
组织蛋白酶D增强胃癌细胞对顺铂敏感性的研究
Cathepsin D Enhancing Sensitivity of Gastric Cancer Cells to Cisplatin
投稿时间:2017-11-13  
DOI:10.11735/j.issn.1004-0242.2018.03.A011
中文关键词:  组织蛋白酶D  顺铂  胃癌
英文关键词:cathepsin D(CTSD )  cisplatin  gastric cancer
基金项目:国家自然科学基金(81472208);中国医学科学院医学与健康科技创新工程(2016-I2M-1-001)
作者单位
黄声凯 国家癌症中心/中国医学科学院北京协和医学院肿瘤医院 
王 佳 煤炭总医院 
李 燕 国家癌症中心/中国医学科学院北京协和医学院肿瘤医院 
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中文摘要:
      摘 要:[目的] 探讨组织蛋白酶D(CTSD)能否增强胃癌细胞对顺铂的敏感性及其机理,从而为临床胃癌的化疗开辟一条新路径。[方法] 通过慢病毒将CTSD及其酶活性失活突变体231N稳定整合到胃癌细胞株MKN45中,运用MTT法、流式细胞术、Western blot等技术,观察转染前后各组肿瘤细胞的存活率、凋亡、凋亡蛋白表达的改变。[结果] 与相同浓度作用下的对照组相比,CTSD、231N联合顺铂对细胞存活率的抑制更明显;与对照组相比,CTSD、231N联合顺铂诱导细胞凋亡能力明显增加;Western blot结果显示,CTSD、231N联合顺铂组cleaved caspase 3、cleaved caspase 9表达增加,而代表死亡受体途径的procaspase 8无变化。[结论] 与单一顺铂作用相比,CTSD、231N联合顺铂抑制MKN45细胞存活率、诱导细胞凋亡能力更强,这一作用是通过线粒体途径发挥作用的。
英文摘要:
      Abstract:[Purpose] To investigate the effect of cathepsin D(CTSD) on the chemosensitivity of gastric cancer cells to cisplatin.[Methods] CTSD and its mutation 231N were transfected into gastric cancer MKN45 cells by lentivirus. The cell proliferation was determined by MTT and the expression of apoptosis related proteins was tested by Western blot. The apoptosis rate was detected by flow cytometry. [Results] Compared to cisplatin alone,CTSD or 231N combined with cisplatin inhibited cell proliferation and enhanced cell apoptosis more markedly. Western blotting results indicated that the expression levels of cleaved caspase 3,cleaved caspase 9 in CTSD or 231N combined with cisplatin were increased,however,there were no significant changes in expression of procaspase 8. [Conclusion] CTSD and 231N can increase the inhibition effect of cisplatin on gastric cancer MKN45 cells and enhance cell apoptosis,which may be associated with mitochondrial pathway.
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