Antagonism of Taxol Cytotoxicity by Prolactin: Implication for Patient Resistance to Chemotherapy

摘要

The objective of this investigation is to examine the protective effects of prolactin (PRL) against anti-cancer drugs. Three specific aims were formulated: (1) To characterize the protective effects of PRL against several anticancer drugs, (2) To determine anti-apoptotic mechanism(s), and (3) To examine the protective effects of PRL in vivo. Good progress has been made in all objectives as follows. First, we have shown the protective effects of PRL against taxol, cisplatin and vinblastine in more than one breast cancer cell line. Two, we identified increased activity of a detoxification enzyme as the mechanism by which PRL antagonizes the cytotoxic effects of cisplatin. Ongoing studies are examining to what extent this mechanism of chemoresistance applies to other cytotoxic drugs. Future research will also examine the roles of circulating and breast-derived PRL in the resistance to chemotherapy in live animals.