Role of radiotherapy combined with halofuginone in enhancing therapeutic effect on Lewis lung cancer transplanted in mice and related mechanisms

Abstract

Objective To investigate the role of radiotherapy combined with halofuginone in enhancing the therapeutic effect on Lewis lung cancer (LLC) and influence on tumor invasion and metastasis, and to explore possible molecular mechanisms. Methods The model mice with LLC xenograft were randomly divided into blank control group, halofuginone group, irradiation group, and combination group. On day 3 after the treatment ended, 4 mice in each group were randomly sacrificed, and immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed. The other mice were observed for survival time and liver/lung metastases. Analysis of variance was applied for comparison of results between groups. Results On the ninth day of treatment, the mean tumor volume was 175.2 mm3 in the blank control group, 118.5 mm3 in the halofuginone group, 106.6 mm3 in the irradiation group, and 85.6 mm3 in the combination group (P=0.000). The median survival times for these groups were 39 days, 61.5 days, 78.5 days, and 84.5 days, respectively (P=0.002). The combination group had the lowest number of liver and lung metastases. The results of immunohistochemistry and ELISA showed that compared with the blank control group, the irradiation group had a higher level of transforming growth factor-β1(TGF-β1), while the combination group had a lower level of TGF-β1. The combination group had a lower mean tumor vascular density than the blank control group. The blank control group and the irradiation group had higher expression levels of collagen, while the halofuginone group and the combination group had lower expression levels of collagen. Conclusions Radiotherapy combined with halofuginone may enhance the effect of antitumor therapies, and potential mechanisms still need further investigation. Key words: Transforming growth factor; Irradiation; Halofuginone; Lewis lung neoplasms; Transplanted tumor in mice