VEGF-targeted short hairpin RNA inhibits intraperitoneal ovarian cancer growth in nude mice.
OBJECTIVE
In this study, we inhibited the expression of VEGF by short hairpin RNA (shRNA) in SKOV3 ovarian cancer cells in vitro and in vivo to explore the antitumor efficacy of shRNA in ovarian cancer cells.


METHODS
ShRNA targeting VEGF was cloned into pGenesil-2 plasmid vector and then transfected into SKOV3 ovarian cancer cells using liposome. Silencing of VEGF expression was measured by RT-PCR and ELISA assays. Furthermore, the growth inhibition capacity of shRNA on SKOV3 intraperitoneal ovarian carcinomatosis was tested in nude mice. Tumor weight was measured. Microvessel density, number of apoptotic cells and proliferation index in tumor tissues were assessed by CD31, TUNEL and PCNA immunostaining.


RESULTS
shRNA targeting VEGF significantly silenced VEGF expression in SKOV3 ovarian cancer cells, confirmed by RT-PCR and ELISA assays (p < 0.05). In vivo, the shRNA reduced tumor weight by approximately 60.3% compared with control groups (p < 0.05), accompanied with angiogenesis inhibition (p < 0.01) and apoptosis induction (p < 0.01).


CONCLUSIONS
Our data indicated that shRNA-mediated silencing of VEGF might be a promising therapeutic strategy against ovarian cancer by reducing angiogenesis and inducing apoptosis.
Department of Gynecology and Obstetrics, West China Second Hospital, Chengdu, PR China.
Yu
Y
Bai
Hongxin
H
Deng
Yang
Y
Yang
Xia
X
Zhao
Yuquan
Y
Wei
Gang
G
Xie
Zhengyu
Z
Li
Xiancheng
X
Chen
Lijuan
L
Chen
Yongsheng
Y
Wang
Dan
D
Su
Zhiyong
Z
Qian
Qian
Q
Zhong
Hong
H
Luo
Tao
T
Yi
D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000628:therapy; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A