CLC number: R735.3+5
On-line Access: 2016-09-07
Received: 2016-06-10
Revision Accepted: 2016-08-08
Crosschecked: 2016-08-11
Cited: 2
Clicked: 4969
Jian-zhen Shan, Yan-yan Xuan, Qi Zhang, Jian-jin Huang. Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α[J]. Journal of Zhejiang University Science B, 2016, 17(9): 672-682.
@article{title="Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α",
author="Jian-zhen Shan, Yan-yan Xuan, Qi Zhang, Jian-jin Huang",
journal="Journal of Zhejiang University Science B",
volume="17",
number="9",
pages="672-682",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1600266"
}
%0 Journal Article
%T Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α
%A Jian-zhen Shan
%A Yan-yan Xuan
%A Qi Zhang
%A Jian-jin Huang
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 9
%P 672-682
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1600266
TY - JOUR
T1 - Ursolic acid sensitized colon cancer cells to chemotherapy under hypoxia by inhibiting MDR1 through HIF-1α
A1 - Jian-zhen Shan
A1 - Yan-yan Xuan
A1 - Qi Zhang
A1 - Jian-jin Huang
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 9
SP - 672
EP - 682
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1600266
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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