Anti-tumour effects of small interfering RNA targeting anion exchanger 1 in experimental gastric cancer
Anti-tumour effects of small interfering RNA targeting anion exchanger 1 in experimental gastric cancer
复制标题
靶向阴离子交换器 1 的小干扰 RNA 在实验性胃癌中的抗肿瘤作用。
DOI：
10.1111/j.1476-5381.2011.01521.x
复制
发表时间：
2012-01-01
影响因子：
7.3
通讯作者：
Fu, Guo-Hui
中科院分区：
文献类型：
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作者：
Suo, Wen-Hao;Zhang, Ning;Fu, Guo-Hui
背景和目的阴离子交换蛋白1（AE 1）是在红细胞中发现的一种整合的膜蛋白。我们前期的研究表明，AE 1在人胃癌细胞中表达，并可能参与胃癌的发生。在本研究中，我们进一步研究了AE 1在胃癌发生中的作用和AE 1靶向的小干扰RNA（siRNA）在两种实验性胃癌模型中的抗肿瘤作用。实验方法通过分子和细胞实验来阐明AE 1在胃上皮恶性转化中的作用和AE 1靶向的siRNA对胃癌细胞的作用。在两种小鼠模型中评估了siRNA的体内抗肿瘤作用，即植入人胃癌异种移植物的裸鼠（模型I）和由N-甲基-N-亚硝基脲（MNU）和幽门螺杆菌诱导的胃癌小鼠（模型II）。AE 1靶向siRNA显著抑制AE 1表达并阻碍肿瘤生长。此外，siRNA显着降低了胃癌的检出率，在平行增加不典型增生的实验结束时，在模型II。结论和意义敲低AE 1在胃粘膜中的表达，通过管理合成的siRNA显着抑制胃癌的生长，并降低了这种肿瘤的检测率在实验小鼠。这些结果表明，AE 1是一个潜在的治疗靶点，沉默胃粘膜中AE 1的表达可能为胃癌的治疗提供一种新的治疗方法。缩写AB-PAS，阿新蓝-高碘酸-希夫; AE 1，阴离子交换剂1; DMEM，杜氏改良伊格尔培养基; FBS，胎牛血清; H&E染色，苏木精和伊红染色; H.幽门螺杆菌，幽门螺杆菌; MNU，N-甲基-N-亚硝基脲; MTT，3-（4，5）-二甲基噻唑（-z-y1）-3，5-二苯基四唑溴化铵; siRNA，小干扰RNA
BACKGROUND AND PURPOSE Anion exchanger 1 (AE1) is an integral membrane protein found in erythrocytes. Our previous studies have demonstrated that AE1 is expressed in human gastric cancer cells and may be involved in the carcinogenesis of cancer. In this study, we further investigated the role of AE1 in gastric carcinogenesis and the anti-tumour effects of AE1-targeted small interfering RNAs (siRNAs) in two experimental models of gastric cancer.EXPERIMENTAL APPROACH Molecular and cellular experiments were performed to elucidate the role of AE1 in the malignant transformation of gastric epithelium and the effects of AE1-targeted siRNAs on gastric cancer cells. The anti-tumour effect of the siRNA was evaluated in vivo in two mouse models, nude mice implanted with human gastric cancer xenografts (Model I) and mice with gastric cancer induced by N-methyl-N-nitrosourea (MNU) and Helicobacter pylori (Model II).KEY RESULTS AE1 was found to increase gastric carcinogenesis by promoting cell proliferation. AE1-targeted siRNA significantly suppressed AE1 expression and hindered tumour growth. Furthermore, the siRNA markedly decreased the detection rate of gastric cancer, in parallel with an increase in atypical hyperplasia at the end of the experiment in Model II.CONCLUSIONS AND IMPLICATIONS Knockdown of AE1 expression in gastric mucosa by administration of synthetic siRNAs significantly inhibits the growth of gastric cancer and decreases the detection rate of this tumour in experimental mice. These results suggest that AE1 is potentially a key therapeutic target and the silencing of AE1 expression in gastric mucosa could provide a new therapeutic approach for treating gastric cancer. Abbreviations AB-PAS, Alcian blue-periodic acid-Schiff; AE1, anion exchanger 1; DMEM, Dulbecco's Modified Eagles Medium; FBS, fetal bovine serum; H&E staining, haematoxylin and eosin stain; H. pylori, Helicobacter pylori; MNU, N-methyl-N-nitrosourea; MTT, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide; siRNA, small interfering RNA