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Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
Published on: January 4, 2012
Effect of recombinant adenovirus vector mediated human interleukin-24 gene transfection on pancreatic carcinoma
Xin-ting Pan1, Qing-yun Zhu, De-chun Li
1Department of General Surgery, First Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215006, China.
Background:
Pancreatic cancer is a highly malignant tumor affecting an ever increasing number of patients with a mean 5-year survival rate below 4%. Therefore, gene therapy for cancer has become a potential novel therapeutic modality. In this study we sought to determine the inhibitory effects of adenovirus-mediated human interleukin-24 (AdhIL-24) on pancreatic cancer.
Methods:
Human interleukin-24 gene was cloned into replication-defective adenovirus specific for patu8988 tumor cells by virus recombination technology. Reverse transcription-polymerase chain reaction and Western blotting analysis were used to determine the expression of human interleukin-24 mRNA in patu8988 cells in vitro. Induction of apoptosis by overexpression of human interleukin-24 in patu8988 cells was determined by flow cytometry. In vivo efficacy of adenoviral delivery of human interleukin-24 was assessed in nude mice (n = 10 for each group) bearing patu8988 pancreatic cancer cell lines by determining inhibition of tumor growth, endothelial growth factor and CD34 expression, and intratumoral microvessel density (MVD).
Results:
The recombinant adenovirus vector AdVGFP/IL-24 was constructed with a packaged recombinant retrovirus titer of 1.0 x 10(10) pfu/ml and successfully expressed of both mRNA and protein in patu8988 cells. The AdVGFP/IL-24 induced apoptosis of patu8988 tumor cells in vitro and significantly inhibited tumor growth in vivo (P < 0.05). The intratumoral MVD decreased significantly in the treated tumors (P < 0.05).
Conclusion:
The recombinant adenovirus AdGFP/IL-24 can effectively express biologically active human interleukin-24, which results in inhibition of pancreatic cancer growth.
Insights
Adenovirus-mediated human interleukin-24 (AdhIL-24) gene therapy effectively inhibits pancreatic cancer growth. This novel approach induces apoptosis and reduces tumor vascularization, offering a promising new treatment strategy for this deadly disease.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Pancreatic cancer has a low survival rate, necessitating novel therapeutic strategies.
- Gene therapy presents a potential new modality for treating cancer.
- This study investigated the efficacy of adenovirus-mediated human interleukin-24 (AdhIL-24) in pancreatic cancer.
Purpose of the Study:
- To evaluate the inhibitory effects of AdhIL-24 on pancreatic cancer.
- To assess the gene therapy's potential as a novel treatment for pancreatic cancer.
Main Methods:
- Constructed a replication-defective adenovirus vector (AdVGFP/IL-24) for human interleukin-24 delivery.
- Utilized RT-PCR and Western blotting to confirm gene expression in patu8988 cells.
- Assessed in vitro apoptosis via flow cytometry and in vivo tumor growth inhibition, MVD, and angiogenesis markers in nude mice models.
Main Results:
- Successfully constructed and expressed AdVGFP/IL-24 in patu8988 cells at both mRNA and protein levels.
- Demonstrated significant in vitro apoptosis induction and in vivo tumor growth inhibition (P < 0.05).
- Observed a significant decrease in intratumoral microvessel density (MVD) in treated tumors (P < 0.05).
Conclusions:
- The recombinant adenovirus AdGFP/IL-24 effectively expresses biologically active human interleukin-24.
- AdhIL-24 demonstrates significant potential in inhibiting pancreatic cancer growth.
- This gene therapy approach warrants further investigation for pancreatic cancer treatment.

