Background: The beneficial antitumor effects of low-molecular-weight heparins (LMWHs) have previously been investigated in basic and clinical studies. In this study, the antitumor efficacy of nadroparin combined with radiotherapy was investigated in vivo.
Methods: A total of 48 tumor-bearing mice were randomly divided into six groups (n=8 per group): control group, irradiation group (X), LMWH_1,000 group, LMWH_2,000 group, LMWH_1,000+ X group and LMWH_2,000+X group. Following this, tumor growth, weight and inhibitory rate, as well as the survival of mice in each group, were determined. Levels of serum interleukin (IL)-6 and transforming growth factor (TGF)-β1 were determined via enzyme-linked immunosorbent assay (ELISA) analyses. The expression levels of CD34 were investigated using immunohistochemistry analyses to represent the microvascular density (MVD) values of tumor tissues. In addition, tumor cell apoptosis was investigated using TdT-mediated dUTP nick end labeling (TUNEL) analysis post treatment. The expression levels of survivin were analyzed by Western blotting.
Results: The volumes and weights of tumors in the treatment groups were demonstrated to be significantly decreased, which was most obvious in the LMWH_2,000+X group. The tumor inhibitory rate was significantly increased in the treated mice. ELISA assays demonstrated that the concentrations of serum IL-6 and TGF-β1 were significantly decreased in the LMWH_2,000+ X group. In addition, the decreased CD34 expression was found in the combined treatment groups. TUNEL assays demonstrated that the apoptosis rate was increased in treated mice, and the highest apoptosis rate was exhibited by the LMWH_2,000+X group. Results of Western blotting demonstrated that combinatory treatment with both nadroparin and X-ray irradiation significantly inhibited the expression of survivin.
Conclusion: These results demonstrated that a combinatory treatment strategy of nadroparin with fractionated irradiation had a strong synergistic antitumor effect in vivo, which may be associated with the promotion of apoptosis, inhibited secretion of TGF-β1 and IL-6 and downregulation of CD34 and survivin expression.
Keywords: low-molecular-weight heparins, Lewis lung cancer, X-ray irradiation, microvascular density