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.

Abstract

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.

• Authors: Fan Yang, Zhengyu Li, Hongxin Deng, Hanshuo Yang, Fei Yan, Zhiyong Qian, Lijuan Chen, Yuquan Wei, Xia Zhao
• Journal: Oncology (Oncology) Vol. 75 Issue 3-4 Pg. 137-44 ( 2008) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 18824876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2008 S. Karger AG, Basel.

Chemical References

• Apoptosis Regulatory Proteins
• Liposomes
• RNA, Messenger
• Recombinant Proteins

Topics

• Animals
• Apoptosis (physiology)
• Apoptosis Regulatory Proteins (genetics)
• Cell Proliferation
• Female
• Gene Transfer Techniques
• Genetic Therapy
• Humans
• In Situ Nick-End Labeling
• In Vitro Techniques
• Liposomes
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neovascularization, Pathologic (prevention & control)
• Ovarian Neoplasms (genetics, mortality, therapy)
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Survival Rate
• Transfection
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays