title: Suppressive effect of 19-nor-1α-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model.
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.
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Mi Ra
authors.initials: MR
authors.lastname: Park
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Myung Suk
authors.initials: MS
authors.lastname: Park
authors.forename: Jun Eul
authors.initials: JE
authors.lastname: Hwang
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Shim
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Cho
authors.forename: Ik-Joo
authors.initials: IJ
authors.lastname: Chung
authors.forename: Woo Kyun
authors.initials: WK
authors.lastname: Bae
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary*; D049268:Positron-Emission Tomography; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004872:Ergocalciferols; D019788:Fluorodeoxyglucose F18; C084656:paricalcitol