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The development of colorectal cancer (CRC) is strongly correlated with the aberrant activation of multiple intracellular signaling transduction cascades including STAT3,Hedgehog,Akt and MAPK pathways which usually function redundantly.In addition,crosstalk between these pathways forms a complicated signaling network that is regulated by compensatory mechanisms.Therefore,most of the currently used and single-target-based anti-tumor agents might not always be therapeutically effective.Moreover,long-term use of these agents often generates drug resistance.These problems highlight the urgent need for the development of novel anti-cancer chemotherapies.Oleanolic acid (OA) is a major active compound present in many medicinal herbs that have long been used for the clinical treatment of CRC.Although previous studies have demonstrated an anti-tumor effect for OA,the precise mechanisms of its tumorcidal activity are not well understood.In the present study,using CRC mouse xenograft model and the human colon carcinoma cell line HT-29,we evaluated the efficacy of OA against tumor growth in vivo and in vitro and investigated the underlying molecular mechanisms.We found that OA inhibits cancer growth without appearant toxicity.Furthermore,OA significantly suppresses the activation of several CRC-related signaling pathways and alters the expression of critical target genes.These molecular effects lead to the induction of apoptosis,inhibition of cellular proliferation,and inhibition of tumor angiogenesis.These data demonstrate that 0A possesses a broad range of anti-cancer activities due to its ability to affect multiple intracellular targets,suggesting that OA could be a novel multi-potent therapeutic agent for cancer treatment.