Document Detail


Resistance to paclitaxel in hepatoma cells is related to static JNK activation and prohibition into entry of mitosis.
MedLine Citation:
PMID:  22323130     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hepatocellular carcinoma (HCC) generally shows chemoresistant features to anti-cancer agents. Paclitaxel has been clinically used in the treatment of various cancers. However, effect of paclitaxel on HCC has not been adequately addressed. Here, we found two categories of hepatoma cells in response to paclitaxel. Paclitaxel effectively decreased the cell viability of SNU475, Hep3B, and SNU387 HCC cells and Chang liver cells (death-prone). In contrast, the other 5 hepatoma cell lines (SNU449, SNU398, SUN368, SNU354 and HepG2 cells) were resistant to paclitaxel (death-reluctant). In response to paclitaxel, Bcl-2 was highly phosphorylated in death-prone cells whereas much less portion of Bcl-2 was phosphorylated in death-reluctant cells. Co-treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), significantly reduced the phosphorylated Bcl-2 in death-prone cells and caused a significant reduction in cell death. The reduced cell death was due to prohibition into mitotic entry as evidenced by low cyclinB(1)/Cdk1 kinase activity. In death-reluctant cells, inbuild-phospho-JNK levels were high but no longer activated in response to paclitaxel. We found that paclitaxel combined with caffeine or UCN-01, inhibitors of G(2) DNA damage checkpoint, was able to partially overcome resistance to paclitaxel in these cells. Thus, our data provide the molecular basis of paclitaxel resistance in hepatoma cells and appropriate combination therapy may increase treatment efficacy.
Authors:
Sunyoung Chae; Young Bae Kim; Jong-Soo Lee; Hyeseong Cho
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-9
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  -     ISSN:  1522-1547     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Ajou University School of Medicine.
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