The Effect of Analogues of 1α,25-Dihydroxyvitamin D2 on the Regrowth and Gene Expression of Human Colon Cancer Cells Refractory to 5-Fluorouracil
PBN-AR
Instytucja
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie – Państwowy Instytut Badawczy
Informacje podstawowe
Główny język publikacji
en
Czasopismo
International Journal of Molecular Sciences
ISSN
1422-0067
EISSN
Wydawca
DOI
URL
Rok publikacji
2016
Numer zeszytu
6
Strony od-do
903-903
Numer tomu
17
Identyfikator DOI
Liczba arkuszy
0.3
Słowa kluczowe
en
1α,25-dihydroxyvitamin D2; 1α,25-dihydroxyvitamin D3; vitamin D analogues; vitamin D and chemotherapy; cancer and vitamin D; cancer stem cell; colorectal cancer; HT-29 cell line
Streszczenia
Język
en
Treść
This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU). All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917), as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916) were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917) and the analogue of 1,25D3 (PRI-2191) might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy.
Inne
System-identifier
COI88e53cd4a44c464792deadf08df1bf15
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