Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells.
Retinoids and vitamin D are important factors that regulate cellular growth and differentiation. An additive growth-inhibitory effect of retinoids and vitamin D analogues has been demonstrated for human myeloma, leukaemic and breast cancer cells. We set out to study the effects of the vitamin D analogue EB1089 and the retinoids all-trans- and 9-cis-retinoic acid on the human pancreatic adenocarcinoma cell lines Capan 1 and Capan 2 and the undifferentiated pancreatic carcinoma cell line Hs766T. The cell lines investigated expressed vitamin D receptor, retinoic acid receptor (RAR)-alpha and gamma as determined by polymerase chain reaction after reverse transcription. RAR-beta was expressed only in Hs766T cells. Addition of all-trans-retinoic acid increased the amount of RAR-alpha mRNA in the three cell lines and induced RAR-beta mRNA in Capan 1 and Capan 2 cells. All-trans-retinoic acid at a concentration of 10 nM inhibited the growth of Capan 1 and Capan 2 cells by 40% relative to controls. 9-cis-Retinoic acid was less effective. Neither all-trans-retinoic acid nor 9-cis-retinoic acid affected the growth of Hs766T cells. EB1089, if added alone to the cells, did not significantly inhibit growth. However, the combination of 1 nM EB1089 with 10 nM all-trans-retinoic acid exerted a growth-inhibitory effect of 90% in Capan 1 cells and of 70% in Capan 2 cells. Our data suggest that vitamin D analogues together with retinoids inhibit the growth of human pancreatic cancer cells. However, in vivo studies are necessary to examine the potential use of retinoids and vitamin D analogues on pancreatic cancer.
Zugmaier
G
G
Department of Medical Oncology, Marburg University Medical Center, Germany.
Jäger
R
R
Grage
B
B
Gottardis
M M
MM
Havemann
K
K
Knabbe
C
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D017931:DNA Primers; D007668:Kidney; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D016133:Polymerase Chain Reaction; D051381:Rats; D018167:Receptors, Calcitriol / Q000096:biosynthesis*; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis*; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D000970:Antineoplastic Agents; D017931:DNA Primers; C000607071:RARA protein, human; C000607073:Rara protein, rat; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D001613:beta 2-Microglobulin; C082925:retinoic acid receptor beta; D014212:Tretinoin; D002117:Calcitriol; C078903:seocalcitol