Targeting CD24 for treatment of ovarian cancer by short hairpin RNA.
OBJECTIVE
CD24 is markedly overexpressed in ovarian cancer and plays a critical role in ovarian cancer survival and metastasis, rendering it an interesting target for anti-tumor therapy. Using short hairpin RNA (shRNA) targeting CD24, we aimed to investigate the anti-tumor efficacy of CD24 knockdown in ovarian cancer cells in vitro and in vivo.


METHODS
CD24 shRNA vector (CD24-shRNA) and empty plasmid vector (EP) were transfected into ovarian cancer SKOV3 cells and the knockdown efficacy assessed by Western blot analysis. The effects of CD24 knockdown in SKOV3 cells in vitro, including cell viability and apoptosis, were determined using methyl thiazolyl blue tetrazolium bromide (MTT), flow cytometry and propidium iodide (PI) staining assays. The effects in vivo of CD24 knockdown on angiogenesis, cell proliferation and apoptosis were assessed using immunohistochemistry against CD31, proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assays.


RESULTS
Transfection of CD24-shRNA effectively down-regulated CD24 expression in vitro and in vivo. Administration of CD24-shRNA into nude mice bearing ovarian cancer significantly suppressed tumor volume growth.


CONCLUSIONS
Knockdown of CD24 expression by CD24-shRNA significantly inhibited cell viability and induced apoptosis of SKOV3 cells in vitro. Administration with CD24-shRNA in vivo suppressed tumor volume increase by microvessel density (MVD) decrease, cell proliferation inhibition and apoptosis induction. All the data suggested that knockdown of CD24 by shRNA might be a potential therapeutic approach against human ovarian cancer.
Su
Dan
D
Department of Gynecology and Obstetrics, West China Second Hospital, Chengdu, People's Republic of China.
Deng
HongXin
H
Zhao
Xia
X
Zhang
Xi
X
Chen
LiJuan
L
Chen
XianCheng
X
Li
ZhengYu
Z
Bai
Yu
Y
Wang
YongSheng
Y
Zhong
Qian
Q
Yi
Tao
T
Qian
ZhiYong
Z
Wei
YuQuan
Y
D000818:Animals; D017209:Apoptosis; D051927:CD24 Antigen / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D034741:RNA, Small Interfering / Q000378:metabolism*
D051927:CD24 Antigen; D034741:RNA, Small Interfering