Sildenafil and Phosphodiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumors to Doxorubicin

摘要

The overall goal of this work is to determine the basis for the differential effects of phosphodiesterase inhibitors, such as sildenafil, in terms of protecting cardiac cells and the heart from the toxicity of the antitumor drug adriamycin, while failing to protect the breast tumor cell. In the current work, we have substantiated our previous observations in the breast tumor cell and extended these findings to other chemotherapeutic drugs (taxol and cisplatin) as well as ionizing radiation. However, we have been unable to demonstrate protection from adriamycin in a different model of cardiomyocytes. This may relate to a number of factors that are currently under investigation, including the high concentration of adriamycin used for a prolonged time period as well as the possible absence of phosphodiesterase-5 as a target in these cells. We believe that a more extensive analysis of the nature of the response to sildenafil in these cardiomyocytes will provide insights as to the mechanism(s) of cytoprotection.