Establishment of thFree human pancreatic cancer orthotopic xenograft nude mice models and serum metabolomics

Abstract

Objective To analyze the metabolic profile in serum between normal and orthotopic xenograft nude mice burdened with three human pancreatic cancer cell lines, which were differentiated differently. Methods Human pancreatic cancer lines SW1990, BxPC-3 and Panc-1 were subcutaneously injected into the nude mice, respectively. When the tumor volume reached 1.0 cm3, the nude mice were euthanized and the tumor tissues were removed and implanted to the pancreas to establish the orthotopic xenograft mice model. The serum from three orthotopic xenograft tumor nude mice and the normal controls were collected and then analyzed by 1H nuclear magnetic resonance spectroscopy. Results The three orthotopic xenograft nude mice models were successfully established. In SW1990, BxPC-3 and Panc-1 group, the orthotopic xenograft tumor formation rate was 79% (11/14), 93% (13/14) and 86% (12/14), while the mortality was 7% (1/14), 0 and 7% (1/14), respectively. Compared with control group, the content of metabolites in the serum of orthotopic xenograft tumor nude mice was increased including creatine, alanine, glutamine, 1-methylhistidine, isoleucine, lactate, phenylalanine, tryptophan and valine, but the glycerolphosphocholine (GPC) and glucose levels were reduced. As the tumors progressed to be more malignant, the content of valine and isoleucine tended to increase. Conclusions The establishment of the orthotopic implantation tumor nude mice model was stable and reliable with high tumor formation rate. Obvious metabolic differences of glucose, lipid and amino acids were observed between normal and human pancreatic cancer tumor burdening nude mice models. The common metabolic features identified in all three nude mice models burdened with human pancreatic cancer could be used as the potential markers for diagnosing human pancreatic cancer. Key words: Pancreatic cancer; Metabolomics; H nuclear magnetic resonance; Animal model