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Published on: April 26, 2018
Suppression of tumor growth in xenograft model mice by programmed cell death 4 gene delivery using
1Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
Abstract:
Cancer gene therapy using tumor suppressor genes is considered to be an attractive approach for arresting cell growth and inducing apoptosis. Programmed cell death 4 (Pdcd4) is a tumor suppressor gene, which prevents tumorigenesis and tumor progression. To address the issue of whether expression of PDCD4 protein induces apoptosis in cancerous cells, the Pdcd4 gene was delivered using folate-PEG-baculovirus. Folate-PEG-baculovirus containing Pdcd4 gene (F-P-Bac-Pdcd4) was constructed by attachment of F-PEG to the baculovirus surface using chemical modification. The F-P-Bac-Pdcd4 showed enhanced transduction efficiency, efficiently expressed PDCD4 protein, and induced apoptosis in human epidermal carcinoma (KB) cells as compared with an unmodified baculovirus. In a tumor xenograft study, injection of F-P-Bac-Pdcd4 into tumors established from the KB cell line by subcutaneous implantation significantly suppressed tumor growth and induced apoptosis. Thus, this study shows a new baculovirus-mediated tumor suppressor gene delivery system for cancer therapy.
Insights
This study developed a novel baculovirus delivery system for the tumor suppressor gene Pdcd4 (programmed cell death 4). This enhanced gene therapy effectively induced cancer cell death and suppressed tumor growth in preclinical models.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- Cancer gene therapy aims to halt cancer progression using tumor suppressor genes.
- Programmed cell death 4 (Pdcd4) is a key tumor suppressor gene that inhibits tumorigenesis.
Purpose of the Study:
- To investigate if PDCD4 protein expression induces apoptosis in cancer cells.
- To develop and evaluate a novel baculovirus-mediated gene delivery system for Pdcd4.
Main Methods:
- Constructed folate-PEG-baculovirus containing the Pdcd4 gene (F-P-Bac-Pdcd4) via chemical modification.
- Assessed transduction efficiency and PDCD4 protein expression in human epidermal carcinoma (KB) cells.
- Evaluated tumor growth suppression and apoptosis induction in a KB tumor xenograft model.
Main Results:
- F-P-Bac-Pdcd4 demonstrated enhanced transduction efficiency and efficient PDCD4 protein expression.
- The modified baculovirus induced apoptosis in KB cells more effectively than unmodified baculovirus.
- In vivo studies showed significant suppression of tumor growth and increased apoptosis upon F-P-Bac-Pdcd4 injection.
Conclusions:
- Folate-PEG-baculovirus serves as an effective delivery vehicle for the tumor suppressor gene Pdcd4.
- This baculovirus-mediated gene delivery system shows promise for cancer therapy by inducing apoptosis and suppressing tumor growth.
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