Combination therapy with low molecular weight heparin and Adriamycin results in decreased breast cancer cell metastasis in C3H mice.

Abstract

The aim of this study was to investigate the effect of low molecular weight heparin (LMWH) against breast cancer cell invasion and metastasis in C3H mice and the underlying mechanism. The C3H mouse breast cancer model was established, and the mice were then randomly divided into four groups: normal saline group, LMWH group, Adriamycin positive control group and the combination group (LMWH combined with Adriamycin). Twelve days after inoculation, drug treatment was initiated. During the one-month period of drug administration, tumor growth curves were recorded. At the end of the treatment period, the mice were sacrificed and the solid tumor tissue and lung were removed. Hematoxylin and eosin (H&E) staining was used to observe the overall changes in tumor cell morphology and lung metastasis following the treatment. A terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay was used for detection of apoptosis in tumor cells, and immunohistochemical (IHC) analysis was used to determine the expression of vascular endothelial growth factor (VEGF). The tumor growth curves demonstrated that the overall growth of the combination group was less compared with that of the other three groups, indicating that LMWH inhibited the growth of the tumors. H&E staining showed that the area of tumor cell necrosis in the combination group was significantly greater compared with that in the other groups, and less metastasis was observed in the lung. The results from the TUNEL staining demonstrated that there was an increase in the number of blue-black apoptotic cells, and the expression of VEGF was significantly reduced in the combination group compared with the other three groups. Therefore, this indicates that LMWH, combined with Adriamycin significantly reduced the growth of breast cancer cells in C3H mice. The results suggest that the mechanism may be associated with breast cancer cell apoptosis and inhibition of VEGF expression.