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Downregulation of inhibitor of apoptosis-stimulating protein of p53 inhibits proliferation and promotes apoptosis of gastric cancer cells

机译:下调p53凋亡刺激蛋白抑制剂抑制胃癌细胞增殖并促进其凋亡

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摘要

Gastric cancer (GC) remains one of the leading causes of cancer-associated mortality. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the inhibitory apoptosis-stimulating protein p53 family. The overexpression of iASPP has been detected in several types of tumor in humans. However, the role of iASPP in GC remains to be elucidated. The objectives of the present study were to detect the expression of iASPP in GC and examine the potential role of iASPP in GC cell lines. Using reverse transcription-quantitative polymerase chain reaction and western blot analyses, it was identified that the expression of iASPP in GC tissues and GC cell lines was higher compared with that in adjacent normal tissues and in a normal gastric mucosa cell line (GES-1). To examine the role of iASPP in GC cells, the expression of iASPP was inhibited using a small interfering (si)RNA against iASPP and it was observed that iASPP expression was significantly downregulated. Using MTT assays, colony-formation assays and flow cytometry, it was identified that the inhibition of iASPP was able to significantly inhibit the proliferation and colony forming ability and promote apoptosis in GC cells. To examine the role of iASPP in GC cells in vivo, GC cells, which were infected with iASPP-siRNA or control-siRNA were subcutaneously injected into nude mice. It was identified that downregulation of iASPP significantly inhibited tumor growth in vivo. Thus, iASPP may be a potential molecular target in GC therapy.
机译:胃癌(GC)仍然是癌症相关死亡率的主要原因之一。 p53的凋亡刺激蛋白抑制剂(iASPP)是抑制性凋亡刺激蛋白p53家族的成员。已经在人类的几种类型的肿瘤中检测到iASPP的过表达。但是,iASPP在GC中的作用仍有待阐明。本研究的目的是检测iASPP在GC中的表达,并检查iASPP在GC细胞系中的潜在作用。使用逆转录定量聚合酶链反应和蛋白质印迹分析,可以确定iASPP在GC组织和GC细胞系中的表达高于在邻近正常组织和正常胃黏膜细胞系(GES-1)中的表达。 。为了检查iASPP在GC细胞中的作用,使用了一个针对iASPP的小干扰(si)RNA抑制了iASPP的表达,并且观察到iASPP的表达明显下调。使用MTT分析,集落形成分析和流式细胞仪,可以确定iASPP的抑制能够显着抑制GC细胞的增殖和集落形成能力并促进细胞凋亡。为了检查iASPP在体内GC细胞中的作用,将被iASPP-siRNA或对照-siRNA感染的GC细胞皮下注射到裸鼠中。已经确定,iASPP的下调显着抑制了体内肿瘤的生长。因此,iASPP可能是GC治疗中潜在的分子靶标。

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