Browse > Article
http://dx.doi.org/10.5115/acb.2011.44.3.204

Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma  

Baek, Sung-Min (Department of Anatomy, Pusan National University School of Medicine)
Lee, Young-Suk (Department of Anatomy, Pusan National University School of Medicine)
Shim, Hye-Eun (Department of Anatomy, Pusan National University School of Medicine)
Yoon, Sik (Department of Anatomy, Pusan National University School of Medicine)
Baek, Sun-Yong (Department of Anatomy, Pusan National University School of Medicine)
Kim, Bong-Seon (Department of Anatomy, Pusan National University School of Medicine)
Oh, Sae-Ock (Department of Anatomy, Pusan National University School of Medicine)
Publication Information
Anatomy and Cell Biology / v.44, no.3, 2011 , pp. 204-209 More about this Journal
Abstract
A low serum level of vitamin D has been associated with an increased incidence of gastrointestinal tract cancers. However, the effects of vitamin D3 have not been investigated in gastric cancer and cholangiocarcinoma. In the present study, we found that vitamin D3 treatment significantly suppressed the viability of gastric cancer and cholangiocarcinoma cells. Moreover, vitamin D3 had a synergistic effect with other anti-cancer drugs, such as paclitaxel, adriamycin, and vinblastine, for suppressing cell viability. To determine the underlying mechanism involved in the regulation of viability by vitamin D3, we examined the effects of vitamin D3 on expression of hedgehog signaling target genes, which has been associated with gastric cancer and cholangiocarcinoma. Vitamin D3 treatment decreased the level of mRNA expression of patched1, Gli1, cyclin D1, and Bcl2, suggesting the possibility that vitamin D3 may act through regulation of hedgehog signaling. From the above results, we conclude that vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma.
Keywords
Cholecalciferol; Stomach neoplasms; Cholangiocarcinoma;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Cross HS, Bises G, Lechner D, Manhardt T, Kallay E. The Vitamin D endocrine system of the guts: its possible role in colorectal cancer prevention. J Steroid Biochem Mol Biol 2005;97:121-8.   DOI   ScienceOn
2 Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol 2006;57:234-40.   DOI   ScienceOn
3 Mimori K, Tanaka Y, Yoshinaga K, Masuda T, Yamashita K, Okamoto M, Inoue H, Mori M. Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer. Ann Oncol 2004;15:236-41.   DOI   ScienceOn
4 Albertson DG, Ylstra B, Segraves R, Collins C, Dairkee SH, Kowbel D, Kuo WL, Gray JW, Pinkel D. Quantitative mapping of amplicon structure by array CGH identifies CYP24 as a candidate oncogene. Nat Genet 2000;25:144-6.   DOI   ScienceOn
5 Weiss MM, Snijders AM, Kuipers EJ, Ylstra B, Pinkel D, Meuwissen SG, van Diest PJ, Albertson DG, Meijer GA. Determination of amplicon boundaries at 20q13.2 in tissue samples of human gastric adenocarcinomas by high-resolution microarray comparative genomic hybridization. J Pathol 2003;200:320-6.   DOI   ScienceOn
6 Zinser GM, Suckow M, Welsh J. Vitamin D receptor (VDR) ablation alters carcinogen-induced tumorigenesis in mammary gland, epidermis and lymphoid tissues. J Steroid Biochem Mol Biol 2005;97:153-64.   DOI   ScienceOn
7 Yuasa Y. Control of gut differentiation and intestinal-type gastric carcinogenesis. Nat Rev Cancer 2003;3:592-600.   DOI   ScienceOn
8 Smith MG, Hold GL, Tahara E, El-Omar EM. Cellular and molecular aspects of gastric cancer. World J Gastroenterol 2006;12:2979-90.   DOI
9 Olnes MJ, Erlich R. A review and update on cholangiocarcinoma. Oncology 2004;66:167-79.   DOI   ScienceOn
10 Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol 2004;40:472-7.   DOI   ScienceOn
11 Tahara E. Genetic pathways of two types of gastric cancer. IARC Sci Publ 2004;(157):327-49.
12 Wise C, Pilanthananond M, Perry BF, Alpini G, McNeal M, Glaser SS. Mechanisms of biliary carcinogenesis and growth. World J Gastroenterol 2008;14:2986-9.   DOI   ScienceOn
13 Francis H, Alpini G, DeMorrow S. Recent advances in the regulation of cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol 2010;299:G1-9.   DOI
14 Rashid A. Cellular and molecular biology of biliary tract cancers. Surg Oncol Clin N Am 2002;11:995-1009.   DOI   ScienceOn
15 Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy PA. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003;425:846-51.   DOI   ScienceOn
16 Bruggemann LW, Queiroz KC, Zamani K, van Straaten A, Spek CA, Bijlsma MF. Assessing the efficacy of the hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer. Cancer Biol Ther 2010;10:79-88.   DOI   ScienceOn
17 Bijlsma MF, Spek CA, Zivkovic D, van de Water S, Rezaee F, Peppelenbosch MP. Repression of smoothened by patcheddependent (pro-)vitamin D3 secretion. PLoS Biol 2006;4:e232.   DOI   ScienceOn
18 Han ME, Lee YS, Baek SY, Kim BS, Kim JB, Oh SO. Hedgehog signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2. Int J Mol Sci 2009;10:3033-43.   DOI   ScienceOn
19 Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr 2007;85:6-18.   DOI
20 Jiang J, Hui CC. Hedgehog signaling in development and cancer. Dev Cell 2008;15:801-12.   DOI   ScienceOn
21 Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 1993;75:1417-30.   DOI   ScienceOn
22 Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Geet 1997;16:391-6.   DOI
23 Holick MF. Vitamin D and bone health. J Nutr 1996;126(4 Suppl):1159S-64S.   DOI
24 Deeb KK, Trump DL, Johnson CS. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 2007;7:684-700.   DOI   ScienceOn
25 Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, Goltzman D. Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci U S A 2001;98:7498-503.   DOI   ScienceOn
26 Li YC, Pirro AE, Amling M, Delling G, Baron R, Bronson R, Demay MB. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A 1997;94:9831-5.   DOI   ScienceOn
27 Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham ED. Serum 25-hydroxyvitamin D and colon cancer: eight-year prospective study. Lancet 1989;2:1176-8.
28 Bertone-Johnson ER, Chen WY, Holick MF, Hollis BW, Colditz GA, Willett WC, Hankinson SE. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2005;14:1991-7.   DOI   ScienceOn
29 Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000;11:847-52.   DOI   ScienceOn
30 Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006;98:451-9.   DOI   ScienceOn