title: TanshinoneIIA ameliorates inflammatory microenvironment of colon cancer cells via repression of microRNA-155.
abstract: 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 α (TNF-α) 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.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, PR China. cputjj@hotmail.com
authors.forename: Jiajie
authors.initials: J
authors.lastname: Tu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xing
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Tang
authors.forename: Le
authors.initials: L
authors.lastname: Guo
authors.forename: Tao
authors.initials: T
authors.lastname: Xi
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015394:Molecular Structure; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C021751:tanshinone; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases