Concurrent chemoradiotherapy with low-dose docetaxel inhibits the growth of DU-145 prostate cancer xenografts

Introduction

Concurrent chemoradiotherapy (CCRT) has been widely used during the past decades in clinical trials and has now become a common treatment option in many clinical settings. The present study was designed to evaluate the efficacy of combining radiation with low-dose docetaxel in DU-145 prostate cancer xenograft models.

Methods

Male BALB/c nude mice bearing human DU-145 prostate tumors were assigned to four treatment groups: (1) control, (2) docetaxel (10 mg/kg/week, i.v., ×3 weeks), (3) radiation (2 Gy, q.d. ×5, ×3 weeks), (4) CCRT (the combination of docetaxel and radiation). Treatment efficacy was determined by tumor volume and tumor regression measurements. The extent of apoptosis in tumors in response to treatments was assessed via terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay. In addition, immunohistochemical staining of CD34 was done to quantify microvessel density in the tumors.

Results

Our in vivo studies using DU-145 xenograft models in nude mice showed that CCRT compared to either alone significantly inhibited tumor growth, and the percentages of tumor regression were 32.6, 44.2, and 68.6 % for docetaxel, radiation, and CCRT, respectively. Moreover, CCRT did not significantly affected mice weight as compared to docetaxel or radiation alone. TUNEL assays showed that significantly more apoptotic cells were induced in the tumors treated with CCRT than either treatment alone. Anti-CD34 immunohistochemical staining indicated that CCRT significantly inhibited tumor angiogenesis.

Conclusion

These findings suggest that CCRT with low-dose docetaxel inhibits the growth of DU-145 prostate cancer xenografts, by enhancing apoptosis and suppressing angiogenesis. Based on these preclinical findings, we suggest that CCRT for the treatment of prostate cancer deserves further development.