Abstract:
:Cisplatin is a potent chemotherapeutic drug widely used for the treatment of human cancer. However, its efficacy against hepatocellular carcinoma (HCC) is poor for reasons that remain unclear. We show here that prothymosin-alpha (PTMA) is overexpressed in HCC cell lines. Silencing PTMA using short-hairpin RNA sensitizes HCC cells to cisplatin, while ectopic expression of PTMA induces cell resistance to the drug. Cisplatin inhibits both the JNK pathway and PTMA in a dose-dependent manner. Treatment with a JNK inhibitor also reduces PTMA protein stability and sensitizes HCC cells to cisplatin. Notably, the effects of PTMA silencing and JNK inhibition can be reversed by ectopic expression of PTMA. We show that PTMA silencing induces translocation of proapoptotic Bax to mitochondria and enhances cisplatin-induced cytochrome c release and caspase-9 activation. Conversely, ectopic expression of PTMA reverses these effects. Our results indicate that PTMA is positively regulated by JNK and protects HCC cells against cisplatin-induced cell death. The JNK/PTMA axis may thus represent a novel target for chemotherapy against HCC.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Lin YT,Liu YC,Chao CCdoi
10.1016/j.bcp.2016.10.003subject
Has Abstractpub_date
2016-12-15 00:00:00pages
80-89eissn
0006-2952issn
1873-2968pii
S0006-2952(16)30348-3journal_volume
122pub_type
杂志文章abstract::Antitubulin activities of ansamitocins, maytansine and four maytansinoids which are structurally related to ansamitocins were studied using three reaction systems; inhibition of polymerization of bovine brain tubulin, depolymerization of the once polymerized tubulin, and immunofluorescent staining of cytoplasmic micro...
journal_title:Biochemical pharmacology
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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