ObjectiveTo compare the biological characteristics of three modeling methods to establish human large cell lung cancer (LCLC) NCI-H460 xenograft models in nude mice, and provide an experimental basis for finding a suitable modeling approach for different studies. MethodsCultured NCI-H460 cells, NCI-H460 tumor tissue pieces and tumor homogenate were used respectively to establish subcutaneous tumor models in BALB/c-nu/nu nude mice. The tumor formation rate, tumor weight, doubling time and morphology were observed. Blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (G1u), urea nitrogen (BUN) and creatinine (CREA) were analyzed using an automatic biochemical analyzer. WBC count and classification were determined, and finally the phagocytic activity of macrophages and NK cell activity in vitro were assessed. ResultsThe tumor formation rate, tumor growth rate and uniformity in the cultured cells and tumor homogenate groups were significantly better than those of the tissue transplantation group. Five weeks after inoculation, the blood ALT and AST were significantly increased, while BUN, CREA were significantly lower in all the three groups of tumor-bearing mice, the AST and BUN of the tissue transplantation group were significantly higher than those of the other two groups. However, the Glu of tumor-bearing mice decreased significantly 2 weeks after inoculation. The LYM%, MN% and HGB of the peripheral blood of the three groups were lower than those in the normal control group, and WBC, NEUT%, PLT of the cultured cell and homogenate groups were significantly higher than those of the tissue transplantation group. The immune cell activity of the macrophages and NK cells showed a lowering trend in an order of normal control group>homogenate group>cultured cell group>tissue transplantation group. ConclusionsThe modeling method with cultured cells is controllable in number and uniform of tumor growth. It is suitable for the establishment of different experimental xenograft models. The tissue transplantation can meet the need for the establishment of animal models to serve Chinese anti-cancer drug screening, and the homogenate inoculation method is not recommended. The physiological and immunological characteristics of the mouse models have a close relationship with tumor growth.