Inhibition of lung tumor growth in nude mice by siRNACD31 targeting PECAM-1

被引:14
作者
Ouyang, Jin-Sheng [1 ]
Li, Yu-Ping [1 ]
Chen, Cheng-Shui [1 ]
Chen, Jun-Jie [1 ]
Chen, Tong-Ke [1 ]
Cai, Chang [1 ]
Yang, Li [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Resp Med, Wenzhou 32500, Zhejiang, Peoples R China
关键词
small interfering RNA; platelet endothelial adhesion molecule; vascular endothelial growth factor; carcinoma; tumor microenvironment; NONSMALL CELL LUNG; VASCULAR ENDOTHELIAL-CELLS; ADHESION MOLECULE-1; SIGNALING PATHWAY; IN-VITRO; CANCER; PLATELET; ANGIOGENESIS; CHEMOTHERAPY; BEVACIZUMAB;
D O I
10.3892/ol.2014.2091
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Small interfering RNA (siRNA) provides a promising therapeutic approach in the silencing of disease-causing genes. In the present study, the use of 2'-O-methyl-modified siRNA-cluster of differentiation 31 (siRNA(CD31)), with cationic liposome RNA interference (RNAi)-mate as a carrier, effectively silenced the platelet endothelial cell molecule 1 (PECAM-1) gene of murine hemangioendothelioma cells in vitro. In vivo, 2'-O-methyl-modified siRNA(CD31) carried by RNAi-mate was successfully delivered, targeting the PECAM-1 gene in the vasculature of nude mouse lung carcinoma xenografts. The growth of the lung carcinoma xenografts was inhibited by the 2'-O-methyl-modified siRNA(CD31) and RNAi-mate complexes, and the expression of the PECAM-1 protein was downregulated, with a simultaneous decrease in vascular endothelial growth factor (VEGF) protein in the lung carcinoma xenografts. 2'-O-methyl-modified siRNA(CD31)-RNAi-mate complexes may provide a potential therapeutic strategy in lung carcinoma treatment. The effect of PECAM-1 on VEGF expression may possibly be attributed to the function of PECAM-1 signal transduction.
引用
收藏
页码:33 / 40
页数:8
相关论文
共 41 条
[21]   Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts [J].
Inai, T ;
Mancuso, M ;
Hashizume, H ;
Baffert, F ;
Haskell, A ;
Baluk, P ;
Hu-Lowe, DD ;
Shalinsky, DR ;
Thurston, G ;
Yancopoulos, GD ;
McDonald, DM .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 165 (01) :35-52
[22]   Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy [J].
Kim, Seung Tae ;
Uhm, Ji Eun ;
Lee, Jeeyun ;
Sun, Jong-mu ;
Sohn, Insuk ;
Kim, Seon Woo ;
Jung, Sin-Ho ;
Park, Yeon Hee ;
Ahn, Jin Seok ;
Park, Keunchil ;
Ahn, Myung-Ju .
LUNG CANCER, 2012, 75 (01) :82-88
[23]   Bevacizumab and lung cancer: Eligible patients in daily practice [J].
Lagnien-Gaume, V. ;
Jehl, J. ;
Manzoni, P. ;
Jacoulet, P. ;
Gainet-Brun, M. ;
Metzger, F. ;
Pernet, D. ;
Polio, J. -C. ;
Pugin, J. -F. ;
Corgne, J. ;
Amoros, C. ;
Dalphin, J. -C. ;
Westeel, V. .
REVUE DES MALADIES RESPIRATOIRES, 2011, 28 (01) :25-31
[24]   Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1-dependent activation of PI-3K/Akt and regulation of Bcl-2 family members [J].
Limaye, V ;
Li, XC ;
Hahn, C ;
Xia, P ;
Berndt, MC ;
Vadas, MA ;
Gamble, JR .
BLOOD, 2005, 105 (08) :3169-3177
[25]   Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 binding protein in vascular endothelial cells [J].
Masuda, M ;
Osawa, M ;
Shigematsu, H ;
Harada, N ;
Fujiwara, K .
FEBS LETTERS, 1997, 408 (03) :331-336
[26]  
Masuda Michitaka, 2004, Nihon Yakurigaku Zasshi, V124, P311
[27]   Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro [J].
Müller, AM ;
Hermanns, MI ;
Skrzynski, C ;
Nesslinger, M ;
Müller, KM ;
Kirkpatrick, CJ .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2002, 72 (03) :221-229
[28]   Signal transduction pathways mediated by PECAM-1 - New roles for an old molecule in platelet and vascular cell biology [J].
Newman, PJ ;
Newman, DK .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (06) :953-964
[29]   Mitochondrial ROS-K+ channel signaling pathway regulated secretion of human pulmonary artery endothelial cells [J].
Ouyang, Jin-Sheng ;
Li, Yu-Ping ;
Li, Cheng-Ye ;
Cai, Chang ;
Chen, Cheng-Shui ;
Chen, Shao-Xian ;
Chen, Yan-Fan ;
Yang, Li ;
Xie, Yu-Peng .
FREE RADICAL RESEARCH, 2012, 46 (12) :1437-1445
[30]   PECAM-1 regulates proangiogenic properties of endothelial cells through modulation of cell-cell and cell-matrix interactions [J].
Park, SunYoung ;
DiMaio, Terri A. ;
Scheef, Elizabeth A. ;
Sorenson, Christine M. ;
Sheibani, Nader .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2010, 299 (06) :C1468-C1484