Suppression of the progress of disseminated pancreatic cancer cells by NK4 plasmid DNA released from cationized gelatin microspheres

Purpose. NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as a potent angiogenesis inhibitor. This study is an investigation to evaluate the feasibility of controlled release of NK4 plasmid DNA in suppressing the tumor growth. Controlled release by a biodegradable hydrogel enabled the NK4 plasmid DNA to exert the tumor suppression effects. Methods. Biodegradable cationized gelatin microspheres were prepared for the controlled release of an NK4 plasmid DNA. The cationized gelatin microspheres incorporating NK4 plasmid DNA were subcutaneously injected to tumor-bearing mice to evaluate the suppressive effects on tumor angiogenesis and growth. Results. The cationized gelatin microspheres incorporating NK4 plasmid DNA could release over 28 days as a result of microspheres degradation. The injection of cationized gelatin microspheres incorporating NK4 plasmid DNA into the subcutaneous tissue of mice inoculated with pancreatic cancer cells prolonged their survival time period. An increase in the tumor number was suppressed to a significantly greater extent than free NK4 plasmid DNA. The controlled release of NK4 plasmid DNA suppressed angiogenesis and increased the cell apoptosis in the tumor tissue while it enhanced and prolonged the NK4 protein level in the blood circulation. Conclusions. We conclude that the controlled release technology is promising to enhance the tumor suppression effects of NK4 plasmid DNA.