Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice
Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung cancer metastasis development in mice
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DOI：
10.1158/0008-5472.can-07-2390
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发表时间：
2008-03-15
期刊：
影响因子：
11.2
通讯作者：
Mueller-Tidow, Carsten
中科院分区：
文献类型：
--
作者：
Bulk, Etmar;Hascher, Anoe;Mueller-Tidow, Carsten
远处转移的发展是全世界癌症相关死亡的主要原因。局部治疗后的辅助治疗方法在特定靶点被抑制时最有效。最近，我们发现S100P过度表达是早期非小细胞肺癌(NSCLC)患者转移发展的一个强有力的预测因子。在这里，我们发现S100P的过表达增加了S.C.的血管生成和转移形成。非小细胞肺癌细胞的异种移植。以质粒衍生的短发夹状RNAs(ShRNA)作为特异性辅助治疗。静脉注射。体内注射抗S100P的shRNA可显著降低移植瘤中S100P蛋白的表达，抑制肿瘤血管生成。初次肿瘤切除后8周的转移形成明显减少。S100P靶向shRNA组小鼠肺转移发生率为31%，而对照组小鼠肺转移发生率为%(P<；0.05)。这些发现表明，基于RNA干扰的治疗方法在佐剂环境中可以非常有效。
Development of distant metastasis is the major reason for cancer-related deaths worldwide. Adjuvant therapy approaches after local therapies are most effective when specific targets are inhibited. Recently, we identified S100P overexpression as a strong predictor for metastasis development in early-stage non-small cell lung cancer (NSCLC) patients. Here, we show that S100P overexpression increased angiogenesis in and metastasis formation from s.c. xenotransplants of NSCLC cells. Plasmid-derived short hairpin RNAs (shRNA) were developed as specific adjuvant therapy. I.v. injected shRNA against S100P significantly decreased S100P protein expression in xenograft tumors and inhibited tumor angiogenesis in vivo. Metastasis formation 8 weeks after primary tumor resection was significantly reduced. Lung metastases developed in 31% of mice treated with S100P-targeting shRNAs compared with 64% in control shRNA-treated mice (P < 0.05). These findings suggest that RNA interference-based therapy approaches can be highly effective in the adjuvant setting.