›› 2019, Vol. 39 ›› Issue (1): 33-.doi: 10.3969/j.issn.1674-8115.2019.01.007

• Original article (Basic research) • Previous Articles     Next Articles

Screening of the anti-atherogenic drugsusing THP-1-HIF-1α-HER-Luciferase cell model

QIAN Yu-jun1, QIN Chun-xia1, SUN Li-li1, DING Hua-min1, LI Tie-jun1, 2   

  1. 1. Pharmacy Department, Shanghai Punan Hospital of Pudong New District, Shanghai 200125, China; 2. College of Pharmacy, The Second Military Medical University, Shanghai 200433, China
  • Online:2019-01-28 Published:2019-02-27
  • Supported by:
    Science and Technology Development Fund of Pudong New District of Shanghai, PKJ2015-Y26; Important Weak Subject Construction Project of Health and Family Planning Commission of Pudong New District of Shanghai, PWZbr 2017-16

Abstract: Objective · To screen the anti-atherosclerosis (AS) activity of the compoundsusing THP-1-HIF-1α-HER-Luciferase high-throughput model, and to verify the anti-AS function of the effective compounds. Methods · THP-1-HIF-1α-HER-Luciferase cells were pretreated with different concentrations of compounds (1, 10, and 100 μg/mL) for 2 h, then cultured under hypoxia for 24 h. Luciferase activity of cells was detected and compounds with anti-AS activity were screenedluciferase activity evaluation. THP-1 and U937 cells were pretreated with effective compounds, and then induced for 24 hoxidized low density lipoprotein (OX-LDL). The formation of foam cells was observedoil red staining. The mRNA level of hypoxia-inducible factor 1α (HIF-1α) was detectedreal-time quantitative PCR (qPCR). HIF-1α protein was detectedWestern blotting. Anti-AS activity of effective compounds were evaluated. Results · Among the 200 compounds, 11 compounds could significantly inhibit the increase of luciferase activity in THP-1-HIF-1α-HER-Luciferase cells inducedhypoxia (all P<0.05), and compound numbered 14 (C14) had the most significant inhibitory effect. THP-1 and U937 cells formed foam cells induced for 24 hOX-LDL. However, cells were pretreated with C14 for 2 h, which could significantly inhibit the formation of foam cells inducedOX-LDL. Cells were induced for 24 hOX-LDL, which could significantly increase the of HIF-1α mRNA and protein (all P<0.05), while cells pretreated with C14 could significantly inhibit the increase of HIF-1α mRNA and protein in a gradient-dependent manner (all P<0.05). Conclusion · THP-1-HIF-1α-HER-Luciferase high-throughput model can be reliability used in screening of compounds with anti-AS activity. C14 has the good anti-AS activity characteristics.

Key words: hypoxia-inducible factor 1&, alpha, (HIF-1&, alpha, ), THP-1 cell, U937 cell, foam cell, atherosclerosis (AS)

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