Efficient inhibition of ovarian cancer growth and prolonged survival by transfection with a novel pro-apoptotic gene, hPNAS-4, in a mouse model. In vivo and in vitro results.
OBJECTIVE
We transfected ovarian cancer cells and administered recombinant plasmid encoding hPNAS-4 to nude mice bearing ovarian cancer, aiming to evaluate the effect of hPNAS-4 against ovarian cancer in vitro and in vivo.


METHODS
Ovarian cancer SKOV3 cells were transfected with hPNAS-4-plasmid, and cell proliferation was evaluated by MTT assay; apoptosis was examined by DNA ladder, Hoechst33258 staining and flow-cytometric assays. Nude mice bearing ovarian cancers were treated with hPNAS-4-p/liposome. Tumor growth was determined and survival was recorded. TUNEL assay and microvessel density was assessed to evaluate apoptosis and angiogenesis.


RESULTS
Both inhibition of proliferation (p < 0.05) and induction of apoptosis (p < 0.05) were observed in SKOV3 cells transfected with hPNAS-4-p in vitro. In hPNAS-4-p-treated tumor cells in vivo, tumor growth significantly decreased, while the survival time of tumor-bearing mice was prolonged compared with control groups (p < 0.05). Increased apoptosis of tumor cells and decreased angiogenesis in tumor tissue were also observed.


CONCLUSIONS
Our promising results on the potential antitumor effects of hPNAS-4 on ovarian cancer in vitro and in vivo may be explained, in part, by the induction of apoptosis and inhibition of angiogenesis. Consequently, hPNAS-4 has potential as a new gene therapy for human ovarian cancer.
Yang
Fan
F
Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, PR China.
Li
Zhengyu
Z
Deng
Hongxin
H
Yang
Hanshuo
H
Yan
Fei
F
Qian
Zhiyong
Z
Chen
Lijuan
L
Wei
Yuquan
Y
Zhao
Xia
X
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D049109:Cell Proliferation; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D008081:Liposomes; D012333:RNA, Messenger; D011994:Recombinant Proteins