Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma
Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma
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DOI：
10.3892/or.2011.1149
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发表时间：
2011-04-01
期刊：
影响因子：
4.2
通讯作者：
Huh, Nam-Ho
中科院分区：
文献类型：
--
作者：
Than, Swe Swe;Kataoka, Ken;Huh, Nam-Ho
新的肿瘤抑制基因REIC/Dkk-3的表达水平在许多人类癌症中降低。我们以前已经表明，携带REIC/Dkk-3的腺病毒载体（Ad-REIC）选择性地诱导癌细胞凋亡，并通过ER应激产生旁观者抗肿瘤效应。我们研究了Ad-REIC在硬化性胃癌（SGC）腹膜播散模型中的可能作用。在各种类型的胃癌中，由于腹腔转移的高发生率，SGC仍然与最差的预后相关。我们发现，单次腹腔注射Ad-REIC抑制肿瘤扩散和疾病进展。通过Ad-REIC的免疫调节导致肿瘤结节内自然杀伤细胞的募集。我们的结论是，Ad-REIC基因治疗可能是一个潜在的工具，在组合的方法，以达到治疗效果，在SGC。
Expression levels of the novel tumor suppressor gene REIC/Dkk-3 are reduced in many human cancers. We have previously showed that an adenovirus vector carrying REIC/Dkk-3 (Ad-REIC) induced apoptosis of cancer cells selectively and exerted bystander antitumor effects via ER stress. We examined possible effects of Ad-REIC in a peritoneal dissemination model of scirrhous gastric carcinoma (SGC). Among various types of gastric cancer, SGC continues to be associated with the worst prognosis due to a high incidence of metastases in the peritoneal cavity. We found that a single intraperitoneal injection of Ad-REIC suppressed tumor dissemination and disease progression. Immunomodulation by Ad-REIC led to recruitment of natural killer cells inside tumor nodules. We conclude that Ad-REIC gene therapy may be a potential tool in combinatorial approaches to achieve curative effects in SGC.