Suppressive effect of 19-nor-1α-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model

J Korean Med Sci. 2012 Sep;27(9):1037-43. doi: 10.3346/jkms.2012.27.9.1037. Epub 2012 Aug 22.

Abstract

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (calcitriol), inhibits the growth of several types of human cancer cells in vitro, but its therapeutic use is limited because it causes hypercalcemia. Among its analogs, 19-nor-1,25-dihydroxyvitamin D(2) (paricalcitol), has fewer calcemic effects and exhibits an activity equipotent to that of calcitriol. We assessed the antitumor and anti-inflammatory effects of paricalcitol in gastric cancer cells, and evaluated the potential role of vitamin D in the treatment of peritoneal metastatic gastric cancer. In this study, treatment with paricalcitol inhibited gastric cancer cell growth and induced cell cycle arrest. Paricalcitol also induced apoptosis and showed anti-inflammatory activity. Moreover, the growth of intraperitoneal metastases in vivo was reduced in mice treated with paricalcitol. (18)F-FDG uptake was significantly lower in the paricalcitol group compared to control group (SUV; control group 13.2 ± 5.3 vs paricalcitol group 4.5 ± 3.0). Intraperitoneal tumor volume was significantly lower in paricalcitol treated mice (control group 353.2 ± 22.9 mm(3) vs paricalcitol group 252.0 ± 8.4 mm(3)). These results suggest that the vitamin D analog, paricalcitol, has anticancer activity on gastric cancer cells by regulation of the cell cycle, apoptosis, and inflammation.

Keywords: Apoptosis; Neoplasms; Paricalcitol (19-nor-1α-25-dihydroxyvitamin D2); Stomach.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Ergocalciferols / chemistry
  • Ergocalciferols / pharmacology*
  • Ergocalciferols / therapeutic use
  • Fluorodeoxyglucose F18 / chemistry
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Peritoneal Neoplasms / drug therapy
  • Peritoneal Neoplasms / secondary*
  • Positron-Emission Tomography
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology*
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Ergocalciferols
  • Fluorodeoxyglucose F18
  • paricalcitol