Combined effect of vitamin D-3 analogs and paclitaxel on the growth of MCF-7 breast cancer cells in vivo

Vitamin D-3 analogs and paclitaxel (Taxol) are able to inhibit the in vitro growth of a variety of malignant cells including breast cancer cells. Thes e two compounds decrease growth by different mechanisms and they have nonov erlapping toxicities. We examined the abilities of three vitamin D-3 compou nds to inhibit growth of a human mammary cancer (MCF-7) in BNX triple immun odeficient mice either alone or with Taxol. Vitamin D-3 analogs were 1,25(O H)(2)D-3 (code name, Compound C), 1,25(OH)(2)-16-ene-23-yne-19-nor-26,27-F- 6 -D-3 (Compound LH), and 24a,26a,27a,-trihomo-22,24-diene-1,25(OH)(2)D-3 ( EB1089). At the doses chosen, the antitumor effect of vitamin D-3 analogs a lone was greater than that of Taxol alone, and an additive effect was obser ved when a vitamin D-3 analog and Taxol were administered together. EB1089 was the most potent compound, and the EB1089 plus Taxol was the most active combination, decreasing the tumor mass nearly 4-fold compared to controls. Weight-gain in each of the experimental cohorts at the end of the study wa s less than the control group, but the gain was significantly less in only two experimental groups (those receiving either EB1089 or Compound C plus T axol). None of the animals became hypercalcemic, and their complete blood c ounts, serum electrolyte analyses, and liver and renal functions were all f airly similar and within the normal range. In summary, this combination of a vitamin D-3 analog and Taxol has the potential to be a therapy for breast cancer.