Growth-inhibitory effects of vitamin D analogues and retinoids on human pancreatic cancer cells

Br J Cancer. 1996 Jun;73(11):1341-6. doi: 10.1038/bjc.1996.256.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology
  • Cell Division / drug effects*
  • Cell Line
  • DNA Primers
  • Kidney
  • Molecular Sequence Data
  • Pancreatic Neoplasms
  • Polymerase Chain Reaction
  • Rats
  • Receptors, Calcitriol / biosynthesis*
  • Receptors, Retinoic Acid / biosynthesis*
  • Retinoic Acid Receptor alpha
  • Transcription, Genetic / drug effects
  • Tretinoin / analogs & derivatives
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / biosynthesis

Substances

  • Antineoplastic Agents
  • DNA Primers
  • RARA protein, human
  • Rara protein, rat
  • Receptors, Calcitriol
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • beta 2-Microglobulin
  • retinoic acid receptor beta
  • Tretinoin
  • Calcitriol
  • seocalcitol