Abstract:
BACKGROUND:Cholangiocarcinoma is a devastating disease with a 2% 5-year survival if the disease has spread outside the liver. The enzyme aspartate beta-hydroxylase (ASPH) has been demonstrated to be highly expressed in cholangiocarcinoma but not in normal bile ducts and found to stimulate tumor cell migration. In addition, it was found that targeting ASPH inhibits cholangiocarcinoma malignant progression. However, it is not clear whether targeting ASPH with the small molecule inhibitor MO-I-1182 suppresses cholangiocarcinoma metastasis. The current study aims to study the efficacy of MO-I-1182 in suppressing cholangiocarcinoma metastasis. METHODS:The analysis was performed in vitro and in vivo with a preclinical animal model by using molecular and biochemical strategies to regulate ASPH expression and function. RESULTS:Knockdown of ASPH substantially inhibited cell migration and invasion in two human cholangiocarcinoma cell lines. Targeting ASPH with a small molecule inhibitor suppressed cholangiocarcinoma progression. Molecular mechanism studies demonstrated that knockdown of ASPH subsequently suppressed protein levels of the matrix metalloproteinases. The ASPH knockdown experiments suggest that this enzyme may modulate cholangiocarcinoma metastasis by regulating matrix metalloproteinases expression. Furthermore, using an ASPH inhibitor in a rat cholangiocarcinoma intrahepatic model established with BED-Neu-CL#24 cholangiocarcinoma cells, it was found that targeting ASPH inhibited intrahepatic cholangiocarcinoma metastasis and downstream expression of the matrix metalloproteinases. CONCLUSION:ASPH may modulate cholangiocarcinoma metastasis via matrix metalloproteinases expression. Taken together, targeting ASPH function may inhibit intrahepatic cholangiocarcinoma metastasis and improve survival.
journal_name
Dig Dis Scijournal_title
Digestive diseases and sciencesauthors
Nagaoka K,Ogawa K,Ji C,Cao KY,Bai X,Mulla J,Cheng Z,Wands JR,Huang CKdoi
10.1007/s10620-020-06330-2subject
Has Abstractpub_date
2020-05-22 00:00:00eissn
0163-2116issn
1573-2568pii
10.1007/s10620-020-06330-2pub_type
杂志文章abstract::The question of whether alcohol drinking is a risk factor for fatty liver as shown by ultrasonography was investigated by both cross-sectional and longitudinal approaches in Japanese undergoing a health checkup. In this cross-sectional study, 32,438 males (49.0 +/- 11.9 years old) and 31,009 females (48.2 +/- 11.6 yea...
journal_title:Digestive diseases and sciences
pub_type: 杂志文章
doi:10.1007/s10620-008-0693-0
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journal_title:Digestive diseases and sciences
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doi:10.1007/s10620-006-9666-3
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doi:10.1007/s10620-012-2193-5
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章,评审
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journal_title:Digestive diseases and sciences
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,已发布勘误
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journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章
doi:10.1007/BF01296082
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章,评审
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abstract::With the increasing incidence of hepatocellular carcinoma (HCC) and its high mortality rates, effective treatment options are of urgent need, preferably in a multidisciplinary setting. In the management of those patients, interventional radiologists play a key role. In this article, we reviewed the current literature ...
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journal_title:Digestive diseases and sciences
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::The development of experimental cholecystitis produced by lysophosphatidylcholine is associated with reversal of the normal absorptive characteristics of gallbladder mucosa, resulting in the intraluminal accumulation of water, glycoprotein, and protein. The purpose of the present study was to attempt to ascertain if t...
journal_title:Digestive diseases and sciences
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journal_title:Digestive diseases and sciences
pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00