Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo

Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo
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慢病毒介导的靶向XIAP和生存素的shRNA在体外和体内抑制SW1990胰腺癌细胞增殖

DOI:
10.3892/mmr.2011.472
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发表时间:
2011-07-01
影响因子:
3.4
通讯作者:
Li, Yi-Xiong
Li, Yi-Xiong
中科院分区:
医学4区
文献类型:
--
作者:
Jiang, Chun;Tan, Tan;Li, Yi-Xiong

文献摘要

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本研究的目的是通过检测凋亡抑制蛋白Survivin和XIAP的生物学特性及其在胰腺癌中的表达,探讨其在胰腺癌中的作用。XIAP和Survivin是胰腺癌潜在的治疗靶点,阐明它们与细胞增殖和凋亡的关系可能有助于开发治疗胰腺癌的新方法。用慢病毒感染人胰腺癌SW1990细胞系,进行实时荧光定量聚合酶链式反应(Real-time PCR,RT-PCR)分析,并用Western blotting进行验证。采用四甲基偶氮唑盐比色法、半胱氨酸天冬氨酸氨基转移酶-3/-7活性测定、DAPI染色和致瘤性检测方法,对人胰腺癌SW1990细胞系和慢病毒感染的实验性胰腺癌小鼠移植瘤模型进行了细胞增殖和细胞凋亡的检测。结果表明,XIAP和Survivin蛋白在不同胰腺癌细胞系中的表达存在差异,它们的表达降低导致细胞在体内和体外的增殖受到抑制。这些发现表明,慢病毒介导的针对XIAP和Survivin的基因治疗是治疗胰腺癌的一种潜在和有吸引力的策略。
The aim of this study was to investigate the inhibitor of apoptosis proteins survivin and XIAP in pancreatic cancer by determining their biological characteristics and expression. XIAP and survivin are potential therapeutic targets for pancreatic cancer, and elucidating their association with cell proliferation and apoptosis may lead to the development of novel treatments for this disease. The human pancreatic cancer SW 1990 cell line was infected with lentivirus and then analyzed by real-time PCR, and the results were confirmed by Western blotting. The MTT assay and the determination of caspase-3/-7 activity, DAPI-staining and tumorigenicity were used to measure cell proliferation and apoptosis in the human pancreatic cancer SW 1990 cell line and in an experimental pancreatic cancer mouse xenograft model inoculated with the lentivirus-transfected SW 1990 cells. The results revealed that the XIAP and survivin proteins were differentially expressed among the pancreatic cancer cell lines, and their decreased expression resulted in the inhibition of cell proliferation in vitro as well as in vivo. These findings suggest that lentivirus-mediated gene therapy targeting XIAP and survivin is a potential and attractive strategy for the treatment of pancreatic cancer.