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Published on: May 10, 2017
Dynamic distribution and expression in vivo of human endostatin gene delivered by adenoviral vector
Guo-An He1, Gang Xue, Lin Xiao
1State Key Laboratory of Tumors, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.
Abstract:
Endostatin, a 20-kDa carboxyl-terminal fragment of collagen XVIII, is a potent inhibitor of endothelial cell proliferation and tumor angiogenesis. We have constructed replication-deficient recombinant adenovirus (Ad-rhE), which encoded secreted human endostatin, and our previous studies showed that Ad-rhE had a potent suppression of tumor growth in vivo. In the present study, we investigated the dynamic distribution and expression of human endostatin gene in vivo using fluorogenic real-time quantitative PCR and enzyme-linked immunosorbent assay(ELISA), respectively, with an injection of 2.0 x10(9)pfu of Ad-rhE. After injection, the Ad-rhE DNAs decreased sharply, but lasted a relative long-term at low concentration (10,000--20,000 copies/mg tissues). Whereas the expressed endostatin rose up rapidly, and reached to the top on day 5 after injection of Ad-rhE, and then decreased sharply, but endostatin in tumors sustained to over 9 days at a certain level. Both Ad-rhE DNAs and endostatin mainly enriched in tumors in vivo, and then in livers. These results suggest that endostatin gene delivered by adenoviral vector can generate a high expression in vivo, and both the metabolism pathways of Ad-rhE DNAs and endostatin in vivo are through the systems of livers.
Insights
Adenoviral delivery of endostatin (Ad-rhE) effectively suppresses tumor growth. This study tracked Ad-rhE DNA and endostatin expression, finding sustained levels primarily in tumors and livers.
Area of Science:
- Biotechnology
- Molecular Biology
- Oncology
Background:
- Endostatin, derived from collagen XVIII, inhibits endothelial cell proliferation and tumor angiogenesis.
- Recombinant adenovirus encoding human endostatin (Ad-rhE) has previously demonstrated potent in vivo tumor suppression.
Purpose of the Study:
- To investigate the in vivo dynamic distribution and gene expression of human endostatin delivered via adenoviral vector.
- To quantify the levels and localization of Ad-rhE DNA and expressed endostatin over time.
Main Methods:
- Fluorogenic real-time quantitative PCR to track Ad-rhE DNA distribution.
- Enzyme-linked immunosorbent assay (ELISA) to measure endostatin expression levels.
- Administration of 2.0 x 10^9 pfu of Ad-rhE in vivo.
Main Results:
- Ad-rhE DNA levels decreased sharply post-injection but persisted long-term at low concentrations (10,000-20,000 copies/mg tissue).
- Expressed endostatin peaked on day 5, sustained over 9 days in tumors, and was primarily enriched in tumors and livers.
- Metabolism of Ad-rhE DNA and endostatin occurred primarily via hepatic systems.
Conclusions:
- Adenoviral vector-mediated endostatin gene delivery achieves high in vivo expression.
- Tumors and livers are the primary sites for Ad-rhE DNA and endostatin accumulation and metabolism.
- These findings support the potential of Ad-rhE as a therapeutic strategy for cancer treatment.
