Pyo Jung-Soo, Ko Young San, Kang Guhyun, Kim Dong-Hoon, Kim Woo Ho, Lee Byung Lan, Sohn Jin Hee
Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 78 Saemunan-gil, Jongno-gu, Seoul, 110-746, South Korea.
J Cancer Res Clin Oncol. 2015 Jul;141(7):1181-8. doi: 10.1007/s00432-014-1890-1. Epub 2014 Dec 5.
Bile acids might induce mucin expression and regulate tumor behavior in esophageal and colon cancers. However, little is known about the effect of bile acids on tumor invasiveness of gastric carcinoma (GC). The aim of the current study was to elucidate the mechanisms by which bile acids regulate tumor invasion in GC.
We investigated bile acid-induced MUC2 expression and cell invasion and migration in the cultured GC cell lines, SNU-216, and MKN45. In addition, immunohistochemical analysis of MUC2 and Snail was performed on 389 archival paraffin-embedded tissues of GC to evaluate the correlation of their expression with prognosis.
Deoxycholic acid (DCA), a secondary bile acid, had no effect on the viability of SNU-216 and MKN45 GC cells at low concentrations (0-100 μM), but decreased viability at a higher concentration (200 μM). MKN45 cells showed higher MUC2 expression than SNU-216 cells under basal conditions. DCA treatment upregulated MUC2 mRNA expression in both SNU-216 and MKN45 cells. Expression of Snail and MMP9 was markedly decreased by DCA treatment, and E-cadherin expression was subsequently increased. DCA significantly inhibited invasion and migration of SNU-216 and MKN45 cells. In human GC, MUC2 expression showed a negative correlation with Snail expression (P = 0.021) and a significantly positive correlation with better prognosis (P = 0.023).
Taken together, our data suggest that DCA induced MUC2 expression in GC cells and inhibited tumor invasion and migration. Additionally, MUC2-expressing GCs showed low rates of Snail expression and were associated with a favorable prognosis.
胆汁酸可能诱导黏蛋白表达并调节食管癌和结肠癌的肿瘤行为。然而，关于胆汁酸对胃癌（GC）肿瘤侵袭性的影响知之甚少。本研究的目的是阐明胆汁酸调节GC肿瘤侵袭的机制。
我们研究了胆汁酸诱导培养的GC细胞系SNU - 216和MKN45中MUC2的表达以及细胞侵袭和迁移情况。此外，对389例GC存档石蜡包埋组织进行了MUC2和Snail的免疫组化分析，以评估它们的表达与预后的相关性。
次级胆汁酸脱氧胆酸（DCA）在低浓度（0 - 100μM）时对SNU - 216和MKN45 GC细胞的活力无影响，但在较高浓度（200μM）时降低了细胞活力。在基础条件下，MKN45细胞的MUC2表达高于SNU - 216细胞。DCA处理上调了SNU - 216和MKN45细胞中MUC2 mRNA的表达。DCA处理显著降低了Snail和MMP9的表达，随后E - 钙黏蛋白表达增加。DCA显著抑制了SNU - 216和MKN45细胞的侵袭和迁移。在人类GC中，MUC2表达与Snail表达呈负相关（P = 0.021），与较好的预后呈显著正相关（P = 0.023）。
综上所述，我们的数据表明DCA诱导GC细胞中MUC2表达并抑制肿瘤侵袭和迁移。此外，表达MUC2的GCs显示Snail表达率低且与良好预后相关。
