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  • Title: Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α.
    Author: Shan JZ, Xuan YY, Zhang Q, Huang JJ.
    Journal: J Zhejiang Univ Sci B; 2016 Sep; 17(9):672-82. PubMed ID: 27604859.
    Abstract:
    OBJECTIVE: To explore the efficacy of ursolic acid in sensitizing colon cancer cells to chemotherapy under hypoxia and its underlying mechanisms. METHODS: Three colon cancer cell lines (RKO, LoVo, and SW480) were used as in vitro models. 5-Fluorouracil (5-FU) and oxaliplatin were used as chemotherapeutic drugs. Cell viability and apoptosis were tested to evaluate the sensitivity of colon cancer cells to chemotherapy. The transcription and expression levels of hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and vascular endothelial growth factors (VEGF) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunoblotting. Cycloheximide and MG132 were used to inhibit protein synthesis and degradation, respectively. In vitro tube formation assay was used to evaluate angiogenesis. RESULTS: We demonstrated the chemosensitizing effects of ursolic acid with 5-FU and oxaliplatin in three colon cancer cell lines under hypoxia. This effect was correlated to its inhibition of MDR1 through HIF-1α. Moreover, ursolic acid was capable of inhibiting HIF-1α accumulation with little effects on its constitutional expression in normoxia. In addition, ursolic acid also down-regulated VEGF and inhibited tumor angiogenesis. CONCLUSIONS: Ursolic acid exerted chemosensitizing effects in colon cancer cells under hypoxia by inhibiting HIF-1α accumulation and the subsequent expression of the MDR1 and VEGF.
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