Novel vitamin D3 analog (CB1093) when combined with paclitaxel and cisplatin inhibit growth of MCF-7 human breast cancer cells in vivo.
Vitamin D3 compounds paclitaxel (Taxol) and cisplatin (CDDP, cis-diamminodichloroplatinum) inhibit growth of a variety of malignant cells. We examined the ability of a novel 20-epi-vitamin D3 analog (code name, CB1093), Taxol and CDDP either alone or in combination to inhibit the growth of a human mammary cancer (MCF-7) growing in BNX triple immunodeficient mice. Tumors in control animals demonstrated infiltrating poorly differentiated adenocarcinomas. At the doses chosen, the antitumor effect of Taxol alone was greater than that of either CB1093 or CDDP alone; and additive effects were observed when either CB 1093 + Taxol or CB 1093 + CDDP + Taxol were administered together. The combination of CB 1093 + Taxol + CDDP was most potent, inhibiting tumor weights by nearly 83% compared to control tumors and producing extensive necrosis of the remaining tumor mass. No additive effect occurred by combining either CB1093 + CDDP or Taxol + CDDP compared to Taxol alone. For all cohorts, their complete hematopoietic blood counts, serum electrolyte analyses including serum calciums as well as their liver and renal functions were within the normal range. Extensive histological analyses of the liver, spleen, kidneys, bone marrow, skin and subcutaneous fat pads from these mice showed no abnormalities. In summary, combined therapy with CB1093 (a potent vitamin D3 analog), Taxol and CDDP, which have non-cross reactive toxicities, holds promise in the treatment of patients with breast cancer.
Cedars-Sinai Medical Center/UCLA, School of Medicine, Los Angeles, CA 90048, USA.
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Koshizuka
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Koike
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Kubota
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Said
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Binderup
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Koeffler
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C103436:CB 1093; D002117:Calcitriol; D017239:Paclitaxel; D002945:Cisplatin