Combined effects of 1,25-dihydroxyvitamin D3 and tamoxifen on the growth of MCF-7 and ZR-75-1 human breast cancer cells.
In the present study we assessed the effect of combined treatment with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and tamoxifen (TAM) on the growth of estrogen-responsive (MCF-7) and estrogen-dependent (ZR-75-1) human breast cancer cells. Both basal and 17 beta-estradiol (17 beta-E2)-stimulated growth were studied. 1,25-(OH)2D3 (10(-10)-10(-7) M) time- and dose-dependently inhibited basal growth of MCF-7 cells, with growth arrest at 10(-7) M. Also, 17 beta-E2-stimulated growth of MCF-7 and ZR-75-1 cells was inhibited by 1,25(OH)2D3 in a time- and dose-dependent manner. TAM inhibited 17 beta-E2-stimulated growth of both cell lines and at high concentration (10(-6) M) it also inhibited basal growth of MCF-7 cells. 10(-6) M TAM together with 1,25-(OH)2D3 resulted n a further inhibition of basal (MCF-7 cells) as well as 17 beta-E2-stimulated proliferation (MCF-7 and ZR-75-1 cells) compared to the inhibition by these agents alone. TAM in combination with 10(-7) M 1,25-(OH)2D3 resulted in growth arrest of 17 beta-E2-stimulated growth of MCF-7 cells. The inhibition of basal and 17 beta-E2-stimulated growth of MCF-7 cells was additive at early time points (4 days), but less than additive at later time points (8-10 days). It was demonstrated that with co-treatment of MCF-7 cells an equipotent inhibition of basal growth could be reached with lower concentrations of 1,25-(OH)2D3, compared to treatment with 1,25-(OH)2D3 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Internal Medicine III, Erasmus University Medical School, Rotterdam, The Netherlands.
T
T
Vink-van Wijngaarden
H A
HA
Pols
C J
CJ
Buurman
J C
JC
Birkenhäger
J P
JP
van Leeuwen
D001943:Breast Neoplasms; D002117:Calcitriol / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D013629:Tamoxifen / Q000633:toxicity*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; D004958:Estradiol; D002117:Calcitriol