Wang Feng, Li Hui-Ming, Wang Hui-Ping, Ma Jia-Lie, Chen Xia-Fang, Wei Fang, Yi Miao-Ying, Huang Qian
Experimental Center, First People's Hospital, Medical School, Shanghai Jiaotong University, Shanghai 200080, P.R. China.
Exp Ther Med. 2010 Sep;1(5):899-904. doi: 10.3892/etm.2010.113. Epub 2010 Jul 12.
The growth of solid tumors is highly dependent on the formation of new blood and/or lymph vessels. Furthermore, metastases often disperse via newly formed blood or lymphatic vessels within the tumor, particularly in the case of epithelium-derived tumors. Since vascular endothelial growth factor (VEGF) signaling plays a vital role in angiogenesis and lymphangiogenesis, we used the small interfering RNA (siRNA) approach to selectively down-regulate VEGF-A, VEGF-C or VEGF receptor 3 (VEGFR-3) expression in bladder transitional carcinoma cells derived from T739 mice in an attempt to suppress tumor growth and metastasis in vivo. The synthetic siRNA was introduced into the tumor tissues by in vivo electroporation. The knockdown of VEGF-A, VEGF-C and VEGFR-3 expression significantly delayed tumor growth and reduced tumor metastasis compared to the negative controls. Thus, electroporation-mediated siRNA delivery to block the VEGF signaling pathway may provide a novel approach for the treatment or prevention of solid tumor growth and metastasis.
实体瘤的生长高度依赖于新血管和/或淋巴管的形成。此外，转移灶通常通过肿瘤内新形成的血管或淋巴管扩散，上皮来源的肿瘤尤其如此。由于血管内皮生长因子（VEGF）信号通路在血管生成和淋巴管生成中起着至关重要的作用，我们使用小干扰RNA（siRNA）方法选择性下调源自T739小鼠的膀胱移行癌细胞中VEGF-A、VEGF-C或VEGF受体3（VEGFR-3）的表达，试图在体内抑制肿瘤生长和转移。通过体内电穿孔将合成的siRNA导入肿瘤组织。与阴性对照相比，VEGF-A、VEGF-C和VEGFR-3表达的敲低显著延迟了肿瘤生长并减少了肿瘤转移。因此，电穿孔介导的siRNA递送以阻断VEGF信号通路可能为实体瘤生长和转移的治疗或预防提供一种新方法。
