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ABCC4 基因是胰腺癌治疗的一个有前途的靶点。

The ABCC4 gene is a promising target for pancreatic cancer therapy.

机构信息

Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.

出版信息

Gene. 2012 Jan 10;491(2):194-9. doi: 10.1016/j.gene.2011.09.029. Epub 2011 Oct 2.

Abstract

Pancreatic cancer is a malignant neoplasm of the pancreas that usually has a poor prognosis. The investigation of targets that effectively inhibit pancreatic cancer cell proliferation should provide a fundamental basis for the clinical application of gene therapy. Here, high expression levels of ABCC4 protein in thirty-six pancreatic cancer specimens were quantified using an immunohistochemical assay, and the potential of ABCC4 as a therapeutic target for pancreatic cancer was investigated. Inhibition of ABCC4 expression at the mRNA and protein levels was achieved in Panc-1 and BxPC-3 pancreatic cancer cells infected with a lentivirus expressing an ABCC4 short hairpin RNA (shRNA). The downregulation of ABCC4 expression in Panc-1 and BxPC-3 cells significantly inhibited their proliferation and colony formation in vitro, compared to cells infected with mock control (p<0.05). Moreover, the specific downregulation of ABCC4 led to the accumulation of cells at the G1 phase of the cell cycle. Our findings reveal that the ABCC4 gene promotes pancreatic cancer cell growth and represents a promising target for gene therapy in pancreatic cancer.

摘要

胰腺癌是一种胰腺的恶性肿瘤,通常预后较差。研究能够有效抑制胰腺癌细胞增殖的靶点,应为基因治疗的临床应用提供一个基本的依据。在这里,采用免疫组化检测了 36 份胰腺癌标本中 ABCC4 蛋白的高表达水平,并研究了 ABCC4 作为胰腺癌治疗靶点的可能性。用表达 ABCC4 短发夹 RNA(shRNA)的慢病毒感染 Panc-1 和 BxPC-3 胰腺癌细胞,在 mRNA 和蛋白水平上抑制 ABCC4 的表达。与感染对照 mock 的细胞相比,下调 ABCC4 表达可显著抑制 Panc-1 和 BxPC-3 细胞的体外增殖和集落形成(p<0.05)。此外,ABCC4 的特异性下调导致细胞周期 G1 期的积累。我们的研究结果表明,ABCC4 基因促进胰腺癌细胞的生长,是胰腺癌基因治疗的一个很有前途的靶点。

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