1. Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α.
- Author
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Shan JZ, Xuan YY, Zhang Q, and Huang JJ
- Subjects
- ATP Binding Cassette Transporter, Subfamily B metabolism, Apoptosis, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Cell Survival, Cycloheximide administration & dosage, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Fluorouracil administration & dosage, Human Umbilical Vein Endothelial Cells, Humans, Neovascularization, Pathologic, Organoplatinum Compounds administration & dosage, Oxaliplatin, RNA, Small Interfering metabolism, Real-Time Polymerase Chain Reaction, Vascular Endothelial Growth Factor A metabolism, Ursolic Acid, Antineoplastic Agents chemistry, Colonic Neoplasms drug therapy, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Triterpenes chemistry
- 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., Competing Interests: Compliance with ethics guidelines: Jian-zhen SHAN, Yan-yan XUAN, Qi ZHANG, and Jian-jin HUANG declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.
- Published
- 2016
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