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The effect of 1,25-dihydroxyvitamin D3 on lymphoma cell lines and expression of vitamin D receptor in lymphoma.

Abstract：

:1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxicity is hypercalcaemia. The cellular action of 1,25(OH)2D3 is mediated by binding to an intracellular protein, the vitamin D receptor (VDR). We have evaluated the activity of 1,25(OH)2D3 and its non-calcaemogenic analogue MC903 in the SU-DHL4 and SU-DUL5 B cell lines which carry the 14;18 translocation characteristic of follicular NHL, and also the expression of the VDR in a range of B cell NHLs. Both agents induced differentiation and had an antiproliferative effect on the SU-DHL4 and SU-DUL5 cell lines. However this occurred at a relatively high concentration (10(-7) M) which exceeds the physiological concentration of 1,25(OH)2D3 by approximately 10(3)-10(4)-fold. Expression of the VDR was low in each cell line and in the low grade lymphoma tumour samples. To account for the observed clinical response to 1 alpha OHD3 (alpha-calcidol) in follicular NHL a network is suggested whereby 1,25(OH)2D3 modulates the activity of CD4+T cells which have previously been shown to promote follicle centre cell proliferation. Vitamin D3 analogues may enable serum levels to be achieved which produce a direct action on follicular lymphoma cells without disturbing calcium metabolism.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Hickish T,Cunningham D,Colston K,Millar BC,Sandle J,Mackay AG,Soukop M,Sloane J

doi

10.1038/bjc.1993.406

subject

Has Abstract

pub_date

1993-10-01 00:00:00

pages

668-72

issue

4

eissn

0007-0920

issn

1532-1827

journal_volume

68

pub_type

杂志文章

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