Anat Cell Biol.  2011 Sep;44(3):204-209. 10.5115/acb.2011.44.3.204.

Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma

• Baek S
• Lee YS
• Shim HE
• Yoon S
• Baek SY
• Kim BS
• Oh SO

• KMID: 1447432
• DOI: http://doi.org/10.5115/acb.2011.44.3.204

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.

Keyword

Cholecalciferol; Stomach neoplasms; Cholangiocarcinoma

MeSH Terms

Cell Survival
Cholangiocarcinoma
Cholecalciferol
Cyclin D1
Doxorubicin
Gastrointestinal Neoplasms
Hedgehogs
Incidence
Paclitaxel
RNA, Messenger
Stomach Neoplasms
Vinblastine
Vitamin D
Vitamins
Cholecalciferol
Cyclin D1
Doxorubicin
Paclitaxel
RNA, Messenger
Vinblastine
Vitamin D
Vitamins

Figure

• 

  Fig. 1 Effect of vitamin D3 on gastric cancer cell and cholangiocarcinoma cell viability. SNU1 (A), SNU638 (B), HuCCT1 (C), and SNU1079 (D) cells were treated with the indicated concentrations of vitamin D3 in 96-well plates in the presence of 1% fetal bovine serum. The cells were further incubated for 4 days, and the viability assay was performed. Ethanol (vehicle) or cyclopamine (10 µM) were used as negative and positive controls, respectively. Data are expressed as percent change (mean±SD) compared to the control (*P<0.01, ANOVA followed by Tukey's multiple comparison).

• 

  Fig. 2 Synergistic effect of vitamin D3 with anti-cancer drugs. SNU1 (A) and HuCCT1 (B) cells were treated with paclitaxel (0.5 nM), adriamycin (ADR, 150 nM), or vinblastine (100 nM) with or without vitamin D3 (35 µM) in the presence of 10% fetal bovine serum. The cell viability assay was performed 2 days after treatment. Ethanol (vehicle) was used as the negative control. Data are expressed as percent change (mean±SD) compared to the control (*P<0.01, compared to the single treatment, Student's t-test).

• 

  Fig. 3 Vitamin D3 regulates the expression of Hh signaling target genes. SNU1 (A) and HuCCT1 (B) cells were seeded at 1×105/well in 6-well plates. After 1 day, the cells were treated with 10 µM vitamin D3. One day later, RNA was purified from the cells, and real-time PCR was performed. Ethanol (vehicle) was used as the negative control. Data are expressed as percent change (mean±SD) compared to control (*P<0.01, †P<0.05, Student's t-test).

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