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RNA 干扰沉默 Bcl-2 基因抑制人胆囊癌细胞系 GBC-SD 的体内外生长。

Bcl-2 gene silencing by RNA interference inhibits the growth of the human gallbladder carcinoma cell line GBC-SD in vitro and in vivo.

机构信息

Department of Hepatobiliary Surgery, First Affiliated Hospital of the Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.

出版信息

Oncol Rep. 2013 Aug;30(2):793-800. doi: 10.3892/or.2013.2539. Epub 2013 Jun 12.

Abstract

Gallbladder carcinoma is the most common malignant tumor in the biliary system; however, the underlying mechanisms of tumor initiation, progression and metastasis are not fully understood to date. The B-cell lymphoma/leukemia-2 (Bcl-2) gene, which is highly expressed in gallbladder carcinoma tissue, is one of the most important regulatory factors in cell apoptosis, and plays an important role in the initiation and progression of gallbladder carcinoma. In the present study, we constructed a eukaryotic expression vector of small interference RNA (siRNA) specific to the Bcl-2 gene and transfected it into GBC-SD human gallbladder carcinoma cells. We demonstrated that the constructed Bcl-2 siRNA vector effectively silenced Bcl-2 gene expression in the GBC-SD human gallbladder carcinoma cells, inhibited cell proliferation, induced cell apoptosis, increased chemotherapeutic sensitivity to 5-fluorouracil and inhibited tumor growth in vivo. Collectively, these data reveal an important contribution of Bcl-2 to gallbladder carcinoma. Thus, the use of a synthetic inhibitor of Bcl-2 may be a promising approach for the treatment of gallbladder carcinoma.

摘要

胆囊癌是胆道系统最常见的恶性肿瘤,但肿瘤发生、进展和转移的潜在机制迄今尚未完全阐明。B 细胞淋巴瘤/白血病-2(Bcl-2)基因在胆囊癌组织中高表达,是细胞凋亡最重要的调节因子之一,在胆囊癌的发生和发展中起重要作用。本研究构建了针对 Bcl-2 基因的小干扰 RNA(siRNA)真核表达载体,并转染至 GBC-SD 人胆囊癌细胞。结果表明,构建的 Bcl-2 siRNA 载体可有效沉默 GBC-SD 人胆囊癌细胞中 Bcl-2 基因的表达,抑制细胞增殖,诱导细胞凋亡,增加对 5-氟尿嘧啶的化疗敏感性,并抑制体内肿瘤生长。综上所述,Bcl-2 对胆囊癌的发生有重要贡献。因此,使用 Bcl-2 的合成抑制剂可能是治疗胆囊癌的一种有前途的方法。

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