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学科主题: 药学
题名:
Pseudolaric acid B inhibits inducible cyclooxygenase-2 expression via downregulation of the NF-kappa B pathway in HT-29 cells
作者: Hou, Li; Xu, Bo; Guo, Wei; Ran, Fu-Xiang; Liu, Jing-Tao; Yuan, Xia; Fu, Hong-Zheng; Cui, Jing-Rong
关键词: Keywords Pseudolaric acid B ; Inflammation ; Cyclooxygenase-2 ; Signal transducer and activator of transcription 3 ; Nuclear factor-kappa B
刊名: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
发表日期: 2012-05-01
DOI: 10.1007/s00432-011-1120-z
卷: 138, 期:5, 页:885-896
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: BREAST-CANCER MCF-7 ; COLON-CANCER ; SIGNALING PATHWAY ; ACTIVATION ; STAT3 ; INFLAMMATION ; CARCINOMA ; APOPTOSIS ; GROWTH ; GENE
英文摘要:

Pseudolaric acid B (PAB) is a diterpene acid isolated from the root and trunk bark of Pseudolaric kaempferi Gordon. Previous work has found that PAB has anti-inflammatory and anti-tumor effects in xenograft models of human hepatocellular carcinoma. The aim of this study is to evaluate the correlation between anti-cancer and anti-inflammatory effects of PAB and its molecular mechanisms on HT-29 cells.

Production of prostaglandin E2 (PGE2) in HT-29 cells was evaluated by ELISA. mRNA of cyclooxygenase-2 (COX-2) was analyzed by RT-PCR assay. High-content screening (HCS) method was adopted to detect the cytokine mixture (CM)-induced transcription activity of NF-kappa B and STAT3. Western blotting was used to evaluate the protein expression levels of inflammatory mediators induced by CM. After treatment with PAB in various concentrations, the inhibition rate of cell proliferation was measured with sulforhodamine B assays. For the in vivo studies, tumor-bearing models xenografted with HT-29 cells were developed in nude mice, and following oral administration with PAB, tumor inhibition rate was calculated.

PAB inhibited the PGE2 production in HT-29 cells significantly (P < 0.05) with similar results detected at the COX-2 mRNA level. Furthermore, PAB suppressed the COX-2 protein expression and significant nuclear translocation of NF-kappa B and STAT3 induced by CM, which correlated with a concomitant degradation of I-kappa B and a decrease in constitutive STAT3 phosphorylation (P < 0.05). Moreover, various concentrations of PAB inhibited the proliferation of HT-29 cells in a dose- and time-dependent manner. In vivo, after treatment with PAB for 17 days, the tumor weight of the 50 and 100 mg/kg treated groups was 0.62 +/- A 0.15 and 0.54 +/- A 0.06 g, respectively. When compared to the control group (0.82 +/- A 0.16 g), the inhibition rate of tumor weight was 24.2% at 50 mg/kg (P < 0.05) and 34.7% at 100 mg/kg (P < 0.001).

PAB shows potential anti-cancer activity in HT-29 cells, and its molecular mechanisms are related to the anti-inflammatory action.

语种: 英语
所属项目编号: 2009ZX09301-010
项目资助者: Eleventh Five-Year Plan for National Science and Technology Major Project
WOS记录号: WOS:000302802300018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54057
Appears in Collections:北京大学药学院_期刊论文

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作者单位: Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

Recommended Citation:
Hou, Li,Xu, Bo,Guo, Wei,et al. Pseudolaric acid B inhibits inducible cyclooxygenase-2 expression via downregulation of the NF-kappa B pathway in HT-29 cells[J]. JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY,2012,138(5):885-896.
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