Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model
Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model
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DOI：
10.1038/sj.cgt.7701071
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发表时间：
2007-09-01
影响因子：
6.4
通讯作者：
Kumon, H.
中科院分区：
文献类型：
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作者：
Edamura, K.;Nasu, Y.;Kumon, H.
我们曾报道过Dickkopf（Dkk）基因家族成员REIC/Dkk-3具有抑癌作用。在这项研究中，我们评估了肿瘤内注射与腺病毒载体编码REIC/Dkk-3基因（Ad-REIC）使用原位小鼠前列腺癌模型RM-9细胞的治疗效果。我们还研究了Ad-REIC基因递送的体内抗转移作用和体外抗侵袭作用。我们证明，Ad-REIC治疗抑制前列腺癌的生长和淋巴结转移，并延长小鼠在模型中的生存期。这些治疗反应与肿瘤内细胞凋亡诱导和体外抑制细胞侵袭/迁移以及基质金属蛋白酶-2活性降低一致。因此，我们得出结论，原位Ad-REIC/Dkk-3基因转移可能是一种有前途的治疗前列腺癌的干预方式。
We had previously reported that REIC/Dkk-3, a member of the Dickkopf ( Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene ( Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.