Ovarian cancer treatment with a tumor-targeting and gene expression-controllable lipoplex.

Abstract

Overexpression of folate receptor alpha (FRα) and high telomerase activity are considered to be the characteristics of ovarian cancers. In this study, we developed FRα-targeted lipoplexes loaded with an hTERT promoter-regulated plasmid that encodes a matrix protein (MP) of the vesicular stomatitis virus, F-LP/pMP(2.5), for application in ovarian cancer treatment. We first characterized the pharmaceutical properties of F-LP/pMP(2.5). The efficient expression of the MP-driven hTERT promoter in SKOV-3 cells was determined after an in-vitro transfection assay, which was significantly increased compared with a non-modified LP/pMP(2.5) group. F-LP/pMP(2.5) treatment significantly inhibited the growth of tumors and extended the survival of mice in a SKOV-3 tumor model compared with other groups. Such an anti-tumor effect was due to the increased expression of MP in tumor tissue, which led to the induction of tumor cell apoptosis, inhibition of tumor cell proliferation and suppression of tumor angiogenesis. Furthermore, a preliminary safety evaluation demonstrated a good safety profile of F-LP/pMP(2.5) as a gene therapy agent. Therefore, FRα-targeted lipoplexes with therapeutic gene expression regulated by an hTERT promoter might be a promising gene therapy agent and a potential translational candidate for the clinical treatment of ovarian cancer.

• Authors: Zhi-Yao He, Feng Deng, Xia-Wei Wei, Cui-Cui Ma, Min Luo, Ping Zhang, Ya-Xiong Sang, Xiao Liang, Li Liu, Han-Xiao Qin, Ya-Li Shen, Ting Liu, Yan-Tong Liu, Wei Wang, Yan-Jun Wen, Xia Zhao, Xiao-Ning Zhang, Zhi-Yong Qian, Yu-Quan Wei
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 23764 (Mar 30 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27026065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Viral Matrix Proteins

Topics

• Animals
• Cell Line, Tumor
• Female
• Genetic Therapy
• Humans
• Liposomes
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Ovarian Neoplasms (pathology, therapy)
• Plasmids (genetics)
• Transfection
• Vesiculovirus (genetics)
• Viral Matrix Proteins (genetics)