Potentiation of antitumor activity of mitomycin C by estradiol: studies of human breast carcinoma xenografts serially transplanted into nude mice.
The effect of experimental cancer chemotherapy with mitomycin C (MMC) was studied using three estrogen-receptor (ER)-positive (MCF-7, R-27, and Br-10) and one ER-negative (MX-1) human breast carcinoma xenograft serially transplanted into nude mice, and the effect of estradiol (E2) priming on the antitumor activity of MMC was investigated. Intramuscular injection of E2 at 1 mg/kg changed the ER state and increased the growth fraction detected by flow cytometry, although the growth rate of ER-positive tumors was not effective by E2 priming. MMC suppressed the growth of the four xenografts in a dose-dependent manner. When 1 mg/kg E2 was administered 1 h before MMC treatment, which was given intraperitoneally at a dose of 3 mg/kg, the antitumor activity of MMC was increased in comparison with MMC alone in ER-positive strains, although the effect of MMC on MX-1 was not changed by E2-priming. Priming with E2 at this dose increases the growth fractions of ER-positive breast carcinoma cells, which are sensitive to MMC, resulting in increased antitumor activity of MMC. This E2-primed MMC chemotherapy may be of value in the treatment of ER-positive human breast cancer.
Oka
S
S
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Takeuchi
T
T
Kitajima
M
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000378:metabolism
D011960:Receptors, Estrogen; D004958:Estradiol; D016685:Mitomycin