Analyze The Metabolite Composition Of Serum Samples From Nude Mice With Orthotopic Human Pancreatic Cancer Using 1H NMR Spectroscopy

Objectives: To establish the orthotopic transplantation tumor animal model of human pancreatic cancer cell line SW1990、Bx PC-3 and Panc-1 in nude mice. Collectting the serum of three kinds of nude mice with human pancreatic cancer to detect the metabolite composition using 1H nuclear magnetic resonance spectroscopy.Methods:1.The establishment of the orthotopic nude mice model with human pancreatic cancer :The ectopic implantation animal model of human pancreatic cancer was established by injecting human cancer lines subcutaneously into the nude mice.When the tumors volume reached 1.0cm3,the nude mice were euthanized and the tumors tissues were removed from the nude mice.Then,the orthotopic transplantation tumor animal model of human pancreatic cancer were established by implanting the tumor tissues to the pancreas of the nude mice. 2.Analysis the serum specimen of orthotopic transplantation tumor nude mice model using 1H nuclear magnetic resonance spectroscopy:Collecting the serum of three kinds of nude mice with human pancreatic cancer and the control group,then analysis the serum specimen of the four groups with Varian NMR System 500 MHz.Analysis the NMR spectrum with Mest Re Nova software.Analysis the differences endogenous metabolites between the cancer groups and control group by PCA,PLS-DA and OPLS-DA with SIMCA-P+ software.Results:1.The establishment of the orthotopic nude mice model with human pancreatic cancer: the SW1990 group: the successful from orthotopic transplantation was 79%(11/14), the mortality was 7%(1/14); the Bx PC-3 group:the successful from orthotopic transplantation was 93%(13/14), no mice was died; the Panc-1 group:the successful from orthotopic transplantation was 86%(11/14), the mortality was 7%(1/14). 2.Analysis the serum specimen of orthotopic transplantation tumor animal model using 1H nuclear magnetic resonance spectroscopy: Compared with control group,the content of metabolites in the serum of orthotopic transplantation tumor nude mice models were increased including creatine,alanine, glutamine, 1-methylhistidine,isoleucine, lactate, phenylalanine, tryptophon, valine, but glucose,Glycerolphosphocholine(GPC) were reduced. With the increasing of tumor malignant degree, valine and isoleucine increased more.Conclusions:1.The method to establish the orthotopic transplantation tumor nude mice model was stable and reliable,it has a high success rate. The model would be conveniently used to study the metabolites of pancreatic cancer. 2.Compared with control group,there is a obvious metabolic difference in the three nude mice models with human pancreatic cancer,including glucose,lipid and Amino acids metabolism. 3.There are some same metabolic features in three kinds of nude mice with human pancreatic caner,they can be used as the potential diagnostic markers for human pancreatic cancer. 4.The rise of branched chain amino acid levels in serum may be associated with the differentiation degree of pancreatic cancer.