VEGF-specific siRNAs modified with 2'-deoxy effectively suppress VEGF expression and inhibit growth of nasopharyngeal carcinoma xenograft in a mouse model.
Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2'-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks' treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2'-deoxy can be used as potential agents for tumor therapy.
Chen
ShanYi
S
Shenzhen People's Hospital, Clinical Medical College of Jinan University, Shenzhen 518020, China.
Gao
GuoFeng
G
Chen
Wei
W
Lü
Qing
Q
Tang
Shen
S
Hua
Zhong
Z
Ye
WenBin
W
Gu
DaYong
D
Wang
ShaYan
S
Zhang
YaOu
Y
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000502:physiology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*
D006131:Growth Inhibitors; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A