The Effects of Recombinant Human Erythropoietin and Tamoxifen on Growth and Angiogenesis of Mammary Tumor in Sprague-Dawley Rat

Abstract

Problem statement: Erythropoietin receptor (EPOR) has been detected in breast cancer cells and speculated to be involved in cancer growth, viability and angiogenesis. This has risen suspicious that EPO administration may enhance the severity of cancer. Approach: This study was undertaken to determine the effects of rHuEPO, Tamoxifen and their combination on the growth and angiogenesis of mammary tumor. Female Sprague-Dawley rats were induced to develop mammary tumor through xenograft technique by inoculating 6x105 LCM 2388 cells. Results: Recombinant human erythropoietin, Tamoxifen and Tamoxifen-rHuEPO combination were administered weekly for four weeks and size of tumors was measured weekly. Blood was also collected weekly and serum separated and subjected to ELISA for Matrix Metalloproteinases 2 (MMP-2) and Vascular Endothelial Growth Factor (VEGF), quantification. The animals were sacrificed at the end of experiment and tumor masses excised for histopathological analysis. Results showed no significance difference in the growth of mammary tumor of rats that received rHuEPO compared to the control rats. Interestingly, the combination of rHuEPO and Tamoxifen produced approximately 90% tumor regression from the initial size compared to Tamoxifen alone which showed 70% tumor regression. Quantification of serum angiogenic factors, MMP2 and VEGF of rHuEPO treatment group showed lower concentrations than the control group. Conclusion/Recommendations: Among all groups, Tamoxifen-treated group showed the lowest concentration of the angiogenic factors. The mitotic index of the tumor from all groups were observed to be at low frequency (G1). In conclusion, rHuEPO did not produce any significant promoting effect either on tumor growth, angiogenesis or tumor cell proliferation.