Tumor growth suppression by adenovirus-mediated introduction of a cell growth suppressing gene tob in a pancreatic cancer model
Tumor growth suppression by adenovirus-mediated introduction of a cell growth suppressing gene tob in a pancreatic cancer model
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DOI：
10.1016/j.biopha.2008.04.010
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发表时间：
2009-05-01
影响因子：
7.5
通讯作者：
Eriguchi, Masazumi
中科院分区：
文献类型：
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作者：
Yanagie, Hironobu;Tanabe, Tuyoshi;Eriguchi, Masazumi
TOB（ErbB-2的转换器）是一种与蛋白酪氨酸激酶受体（包括ErbB-2）相互作用的肿瘤抑制因子。将tob基因导入NIH 3 T3细胞导致细胞生长抑制。本研究以胰腺癌细胞株AsPC-1、BxPC-3、SOJ为研究对象，探讨了tob基因在胰腺癌细胞中的表达及其对肿瘤的抑制作用。我们首先测量了所有胰腺癌细胞系中表达的内源性tob mRNA的水平。然后，我们研究了含有tob cDNA的腺病毒载体（Ad-tob载体）对癌细胞系的作用。病毒载体在293细胞中通过转染扩增。载体的滴度为350 × 10（6）pfu/ml。这些癌细胞能够用MOI 20转染而没有腺病毒毒性。Ad-tob载体转染SOJ和AsPC-1细胞后，细胞生长受到抑制。癌症中Ad-tob基因表达的幅度与肿瘤抑制活性相关。我们使用腹膜注射AsPC-1细胞制备胰腺癌腹膜炎模型。在该模型中，16天后在肠系膜处观察到血性腹水和多个肿瘤结节。在腹膜注射2 × 106个AsPC-1细胞4天后，从第5天至第9天给予AdCAtob（50 × 10（6）pfu/天）。与对照组相比，腹腔注射AdCAtob后10天出现肿瘤生长抑制。腹部无肿瘤结节，无血性腹水。这些结果表明，腹腔注射AdCAtob有可能抑制胰腺癌腹膜炎的形成，并可应用于化疗耐药的癌症腹膜炎。(C)2008年，Elsevier Masson SAS。All rights reserved.
TOB (transducer of ErbB-2) is a tumor suppressor that interacts with protein-tyrosine kinase receptors, including ErbB-2. Introduction of the tob gene into NIH3T3 cells results in cell growth suppression. In this study, we evaluated the effect of tob expression in pancreatic cell lines (AsPC-1, BxPC-3, SOJ) and discuss the tumor-suppressing effects of adenoviral vector expressing tob cDNA. We first measured the levels of endogenous tob mRNA being expressed in all pancreatic cancer cell lines. Then, we examined the effect of adenoviral vector containing tob cDNA (Ad-tob vector) on cancer cell lines. The viral vector was expanded with transfection in 293 cells. The titer of the vector was 350 x 10(6) pfu/ml. These cancer cells were able to be transfected with MOI 20 without adenoviral toxicity. The transfection of Ad-tob vector results in growth suppression of SOJ and AsPC-1 cell lines. The magnitude of the expression of the Ad-tob gene in cancer is correlated to tumor suppressive activity. We prepared pancreatic cancer peritonitis models using a peritoneal injection of AsPC-1 cells. In this model, bloody ascites and multiple tumor nodules were seen at the mesentery after 16 days. AdCAtob (50 x 10(6) pfu/day) was administered from day 5 to day 9 after 4 days of peritoneal injection of 2 x 106 AsPC-1 cells. Tumor growth suppression occurred 10 days after peritoneal injection of AdCAtob compared with the control group. There were no tumor nodules in the abdomen and no bloody ascites. These results suggest that the peritoneal injection of AdCAtob has potential to suppress the formation of pancreatic cancer peritonitis, and can be applied for chemotherapy-resistant cancer peritonitis. (C) 2008 Elsevier Masson SAS. All rights reserved.