Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.

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Lithocholic Acid Stimulates IL-8 Expression in Human Colorectal Cancer Cells via Activation of Erk1/2 MAPK and Suppression of STAT3 Activity.

J Cell Biochem. 2017 Mar 01;:

Authors: Nguyen TT, Lian S, Ung TT, Xia Y, Han JY, Jung YD

Abstract
The secondary bile acid lithocholic acid (LCA), an established tumor promoter, has been implicated in colorectal cancer (CRC) metastasis. Overexpression of interleukin-8 (IL-8) has been detected in CRC, and it contributes to poor prognosis. However, the effect of LCA on IL-8 expression is still undefined. In this study, we observed that LCA treatment induced IL-8 expression in CRC HCT116 cells. Pharmacological inhibition and mutagenesis studies indicated that Erk1/2 is critical for LCA-induced IL-8 expression. Furthermore, LCA reduced the phosphorylation of STAT3, and the STAT3 inhibitor Stattic, accelerated LCA-induced IL-8 expression, suggesting that STAT3 is involved in LCA-induced IL-8 expression. Activation of Erk1/2 functioned as an upstream signal of the STAT3 suppression induced by LCA. In conclusion, LCA activated Erk1/2 and in turn, suppressed STAT3 phosphorylation to induce IL-8 expression in HCT116 cells, thus stimulating endothelial cell proliferation and tube like formation.

PMID: 28247965 [PubMed - as supplied by publisher]

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