siRNA targeting of Cdx2 inhibits growth of human gastric cancer MGC-803 cells.
siRNA targeting of Cdx2 inhibits growth of human gastric cancer MGC-803 cells.
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DOI：
10.3748/wjg.v18.i16.1903
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发表时间：
2012-04
影响因子：
4.3
通讯作者：
Xiao-Tong Wang;Yu-bo Xie;Q. Xiao
中科院分区：
文献类型：
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作者：
Xiao-Tong Wang;Yu-bo Xie;Q. Xiao
目的探讨靶向CDX2的小干扰RNA(SiRNA)对人胃癌MGC-803细胞的体内外作用。方法构建重组pSilencer 4.1-CDX2 siRNA载体，体外转染人胃癌MGC-803细胞。筛选出稳定的转染体。应用逆转录聚合酶链式反应(RT-PCR)和Western blotting方法检测了CDX2 siRNA对人胃癌MGC-803细胞生长、增殖、细胞周期、细胞凋亡、迁移和侵袭能力的影响，并观察了细胞内磷酸酶和紧张素同源蛋白(PTEN)、caspase-9和caspase-3的表达。我们还研究了CDX2 siRNA对MGC-803细胞在裸鼠体内生长的影响。结果RT-PCR和Western blotting结果显示，CDX2 siRNA抑制了内源性CDX2的mRNA和蛋白表达。CDX2siRNA显著抑制细胞生长和增殖，阻断细胞周期进入S期，诱导细胞凋亡，降低MGC803细胞的运动能力和侵袭力。体外培养的MGC-803细胞中，CDX2 siRNA还能增加PTEN的表达，并激活caspase-9和caspase-3。此外，靶向CDX2的siRNA在裸鼠体内抑制了MGC-803细胞的生长，促进了肿瘤细胞的凋亡。结论CDX2参与调控人胃癌细胞MGC-803的生长。调控CDX2的表达可能是一种潜在的胃癌治疗策略。
AIM To investigate the effects of small interference RNA (siRNA) targeting of Cdx2 on human gastric cancer MGC-803 cells in vitro and in vivo. METHODS The recombinant pSilencer 4.1-Cdx2 siRNA plasmids were constructed and transfected into gastric cancer MGC-803 cells in vitro. The stable transfectants were selected. The effects of Cdx2 siRNA on growth, proliferation, cell cycle, apoptosis, migration and invasiveness of human gastric cancer MGC-803 cells were evaluated and the expression of phosphatase and tensin homolog (PTEN), caspase-9 and caspase-3 was observed in vitro by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting analysis. We also investigated the effect of Cdx2 siRNA on growth of MGC-803 cells in nude mice in vivo. RESULTS Cdx2 siRNA led to inhibition of endogenous Cdx2 mRNA and protein expression as determined by RT-PCR and Western blotting analysis. Cdx2 siRNA significantly inhibited cell growth and proliferation, blocked entry into the S-phase of the cell cycle, induced cell apoptosis, and reduced the motility and invasion of MGC-803 cells. Cdx2 siRNA also increased PTEN expression, and activated caspase-9 and caspase-3 in MGC-803 cells in vitro . In addition, siRNA targeting of Cdx2 inhibited the growth of MGC-803 cells and promoted tumor cell apoptosis in vivo in nude mice tumor models. CONCLUSION Cdx2 was involved in regulating pro-gression of human gastric cancer cells MGC-803. Manipulation of Cdx2 expression may be a potential therapeutic strategy for gastric cancer.