Inhibiting colorectal carcinoma growth and metastasis by blocking the expression of VEGF using RNA interference.
Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The present study was designed to determine the role of VEGF in tumor growth and metastasis using RNA interference (RNAi) technology. Four small interfering RNA (siRNA) sequences for the VEGF gene were cloned into expression plasmids and transfected into human colorectal carcinoma (CRC) SW620 cells. Stable transfection of these plasmids decreased VEGF protein expression, leading to the potent suppression of tumor cell proliferation, migration, invasion, and angiogenesis in vitro. Furthermore, in subcutaneous and intrasplenic/portal injection models involving athymic nude mice, the tumor growth and metastasis of SW620 cells expressing VEGF siRNA were significantly inhibited compared with untransfected cells or cells transfected with control vector alone. Immunohistochemical analyses of tumor sections revealed a decreased vessel density and decreased VEGF expression in the animals where siRNA against VEGF were expressed. These results indicate that RNAi of VEGF can be an effective antiangiogenic strategy for CRC.
Wang
Shaochuang
S
National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Hunan Province, 410008, People's Republic of China.
Liu
Hui
H
Ren
Lifeng
L
Pan
Yifeng
Y
Zhang
Yangde
Y
D000230:Adenocarcinoma / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010957:Plasmids; D012333:RNA, Messenger; D034741:RNA, Small Interfering / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A