TanshinoneIIA ameliorates inflammatory microenvironment of colon cancer cells via repression of microRNA-155

TanshinoneIIA, an active component derived from a traditional Chinese medicine, has anti-inflammatory and anti-cancer effect However, the mechanisms underlying the interaction between anti-inflammation and anti-cancer of TanshinoneIIA remain elusive. In the present study, a cell model of inflammation between macrophages and colon cancer cells was used. The results showed that TanshinoneIIA inhibited the proliferation of inflammation-related colon cancer cells HCT116 and HT-29 by decreasing the production of inflammatory cytokines tumor necrosis factor a (TNF-alpha) and interleukin 6 (IL-6), which generated by macrophage RAW264.7 cell line. We identified Phosphatidylinositol-3, 4, 5-trisphosphate 5-phosphatase 1 (SHIP1) was a bona fide target of miR-155. TanshinoneIIA restored the down-regulated level of SHIP1 protein after lipopolysaccharide (LPS)-stimulation in RAW264.7 cells. MicroRNA-155 (miR-155) was up-regulated in macrophages, possibly due to the concomitant increase of PU.1, a transcriptional activator of miR-155, accounting for decreased SHIP1. Treatment with TanshinoneIIA prevented increased PU.1 and hence increased miR-155, whereas aspirin could not These findings support that the interruption of signal conduction between activated macrophages and colon cancer cells could be considered as a new therapeutic strategy and miR-155 could be a potential target for the prevention of inflammation-related cancer. (c) 2012 Elsevier B.V. All rights reserved.