Effects of combination estrogen:cyclophosphamide treatment on the growth of the MXT transplantable mammary tumor in the mouse

Abstract

The present studies were done to determine if the growth-promoting properties of estrogen on the MXT transplantable mammary tumor in the mouse would enhance the cytotoxicity of cyclophosphamide. Mice bearing these tumors had beeswax pellets implanted which contained 17 beta-estradiol (0.01 to 1.0 mg/pellet) and/or injected twice weekly with cyclophosphamide (10 to 40 mg/kg body weight in sesame oil) for 4 to 7 weeks. During this time, tumor size [(L + W)/2] and body weights were monitored every 7 to 14 days. The results show that administration of estradiol (0.01 to 1.0 mg/pellet) by implant slightly stimulated tumor growth, and in no case was tumor regression observed in response to the steroid. Likewise, cyclophosphamide treatment alone (10 to 20 mg/kg) failed to inhibit the tumor; however, combined administration of estradiol plus cyclophosphamide (10 to 40 mg/kg) resulted in significant inhibition of tumor growth. This response was time and dose dependent. These results show that while neither compound alone inhibited tumor growth, estradiol and cyclophosphamide are synergistic and completely block the growth of this transplantable mammary tumor in the mouse. The mechanism for this antagonism of mammary tumor growth remains to be resolved; however, we speculate that estradiol stimulates cellular hypertrophy and hyperplasia in these tumors, and under these conditions the cytotoxic effectiveness of cyclophosphamide is enhanced.