Comparative study on anti-cancer effect of digoxin on human lung cancer in nude mice bearing subcutaneously or orthotopicly implanted xenografts / 中国药理学通报

ABSTRACT

Aim To establish subcutaneous and orthotopic transplantation models of human lung cancer in nude mice, and compare the anti-cancer effects of digoxin between the two models. Methods After subcutaneous inoculation of H460 tissues in nude mice, the tumor volume was measured; HE staining and immunohistochemistry were performed; H460-Luc cell suspension was injected into the lung of nude mice toestablish orthotopic tumor model, the in vivo imaging and fluorescence values were recorded, and the tumor lesions in other organs were observed after dissection. Results Compared with control group, the gemcitabine group had a significant anti-tumor effect (P 0.05). HE staining showed that the cell density in each treatment group decreased, and necrosis and/or fibrous hyperplasia were obvious. Immunohistochemistry indicated that the protein expression of p-p38, p-ERK and Nur77 in each treatment group significantly increased in the subcutaneous transplantation model; in the orthotopic transplantation model, the gemcitabine, the middle (P < 0.05) and low dose of digoxin group could inhibit the tumor growth, while the high dose of digoxin group accelerated the development of tumor (P < 0.05). Conclusion Digoxin is more sensitive to orthotopic transplanted tumor than subcutaneous transplanted tumor, anddigoxin may inhibit the tumor growth by up-regulating the expression of p-p38, pERK and Nur77.