The Effect of Recombinant Phosphoglycerate Kinase-1 for Pancreatic Ductal Adenocarcinoma with Model of Micro PET

Pancreatic cancer is rather difficult for early diagnosis and treatment, it is the 10th ~11th rank of cancer for male patients in Taiwan. The overall 5 years survival rate of pancreatic cancer is only 5 to 10%, and the 5 years survival rate of respectable pancreatic cancer is still about 15-20%. The genetic or molecular changes of pancreatic cancer have been studied for years. They provide only partial informations regarding the protein products of mutated or un-regulated genes. We have analyzed protein profiles of pancreatic ductal adenocarcinoma (PDAC) specimens and paired adjacent non-tumor tissues by two-dimensional gel electrophoresis, and identified 21 proteins with enhanced expression in PDAC by mass spectrometry for 4 years. One of the proteins was identified as phosphoglycerate kinase-1 (PGK-1), a glycolytic enzyme also known as a secreted protein participated in angiogenic process. The immunohistochemical analysis of 63 PDAC specimens revealed a moderate to strong expression of PGK-1 in ＞70% of the tumors. The serum levels of PGK-1 determined by ELISA were also significantly higher in PDAC patients. We have also confirmed the proteomic finding in the tumor tissues of patients with pancreatic cancer, and used the human pancreatic cancer cell line purchased from ATCC to study the protein profiles with or without SiRNA of PGK-1 using 2-D electrophoresis and mass spectrometry target protein in the past two years. The results have been sent for publication. The following three years project, we will continuously study PGK-1 with in vivo model. In the first year, we will analyze the vascular density and PGK-1 expression in the tumor after SiRNA knock-down injection for the mice. In the second year, we will compare the growth of pancreatic cancer cells in mice with/without down-regulation of PGK-1 using small-animal PET technique. In the third year, we will study the changes of tumors in nude mice with injection of rhPGK-1 protein in mice under the expression in small animal micro-PET. We hope after the three years study, we can approach the new drug development of PGK-1 protein, and contribute our results to the development of early diagnosis and new therapy for the patients with pancreatic carcinoma.

Project ID:PC9801-2497
External Project ID:NSC97-2314-B182-007-MY3