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P16INK4a expression adenovirus vector to suppress pancreas cancer cell proliferation
S Kobayashi1, H Shirasawa, H Sashiyama
1Second Department of Surgery, Chiba University School of Medicine, Japan. kobayasi@med.m.chiba-u.ac.jp
Abstract:
The prognoses of pancreatic cancer patients have been miserable even after radical surgery, and adjuvant therapy is necessary to improve the surgical results. p16(INK4a) (p16) is tight-binding and inhibitory protein for cyclin-dependent kinase 4 to induce G1 arrest of the cell cycle. p16 gene deletion is frequently identified in human pancreas cancer. The impaired gene function of p16 might be a major factor of the uncontrolled proliferation and malignancy of pancreas cancer cells. In this study, we investigated the effect of adenovirus p16 expression vector for pancreas cancer cell proliferation to clarify whether the vector might be a promising mode to assist the surgical therapy for pancreas cancer. We constructed the adenovirus p16 expression vector AdexCACSp16 by inserting p16 cDNA to a cassette cosmid containing a nearly full-length adenovirus type 5 genome with E1 and E3 deletions. Thereafter, we assessed the activity of AdexCACSp16 to induce p16 gene mRNA expression in pancreas cancer cell line MIAPaCa-2 and to control cell proliferation. AdexCACSp16 induced a high level of p16 gene mRNA expression in MIAPaCa-2 cells with 1 h contact to the cells. The cell proliferation was significantly suppressed by AdexCACSp16 compared with the control adenovirus group. These data indicate that AdexCACSp16 has the potential to induce p16 gene expression and control pancreas cancer cell proliferation and that the adenovirus p16 expression vector AdexCACSp16 might be a possible method of gene therapy to improve the surgical therapeutic results for pancreas cancer.
Insights
Gene therapy using an adenovirus vector expressing the p16 gene effectively suppressed pancreatic cancer cell proliferation. This approach shows promise as an adjuvant therapy to improve surgical outcomes for pancreatic cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Pancreatic cancer prognosis remains poor despite surgery, necessitating effective adjuvant therapies.
- The p16(INK4a) (p16) tumor suppressor gene, crucial for cell cycle regulation, is frequently deleted or inactivated in pancreatic cancers, contributing to uncontrolled cell growth.
Purpose of the Study:
- To investigate the potential of an adenovirus-mediated p16 expression vector (AdexCACSp16) as a gene therapy strategy for pancreatic cancer.
- To assess AdexCACSp16's efficacy in inducing p16 gene expression and controlling pancreatic cancer cell proliferation.
Main Methods:
- Constructed the AdexCACSp16 vector by inserting p16 cDNA into an adenovirus type 5 genome.
- Transduced the human pancreatic cancer cell line MIAPaCa-2 with AdexCACSp16.
- Assessed p16 mRNA expression and cell proliferation rates post-transduction.
Main Results:
- AdexCACSp16 successfully induced high levels of p16 gene mRNA expression in MIAPaCa-2 cells within 1 hour.
- Significant suppression of pancreatic cancer cell proliferation was observed in cells treated with AdexCACSp16 compared to controls.
Conclusions:
- The AdexCACSp16 vector demonstrates potent capability to induce p16 gene expression and inhibit pancreatic cancer cell proliferation.
- Adenovirus-mediated p16 gene therapy represents a potential therapeutic approach to enhance surgical treatment for pancreatic cancer.
