Acetylsalicylic acid strengthens the effects of ANISpm against hepatocellular carcinoma and its molecular mechanism / 药学学报
Acta Pharmaceutica Sinica
; (12): 1045-1050, 2011.
Article
de Zh
| WPRIM
| ID: wpr-233037
Bibliothèque responsable:
WPRO
ABSTRACT
The objective of this study is to examine the effects of ANISpm, a novel polyamine naphthalimide conjugate, with acetylsalicylic acid against hepatocellular carcinoma in vivo and in vitro and elucidate its potential molecular mechanism. The proliferation inhibition was detected by MTT assay. Cell apoptosis, intracellular fluorescence intensity and mitochondrial membrane potential (MMP) were detected by high content screening (HCS) analysis. Polyamines content was analyzed by reverse-phase high performance liquid chromatography Protein expression levels were quantified by Western blotting assay. The combination treatment strongly inhibited cell proliferation, induced cell apoptosis in HepG2 cells and H22 hepatoma cells, which was mediated by enhanced ANISpm uptake via up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) and depression of intracellular polyamine. Furthermore, this synergistic apoptosis was involved in mitochondria and death-receptor signal pathway. All these findings demonstrated that the combination treatment with acetylsalicylic acid and ANISpm resulted in synergistic antitumor effects on hepatoma cells. Thus, combination therapy with these agents may be useful as a potential template for the development of better chemotherapeutic strategy against hepatoma.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Anatomopathologie
/
Pharmacologie
/
Polyamines
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Acetyltransferases
/
Répartition aléatoire
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Spermine
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Régulation positive
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Acide acétylsalicylique
/
Apoptose
/
Lignée cellulaire tumorale
Type d'étude:
Clinical_trials
Limites du sujet:
Animals
/
Female
/
Humans
langue:
Zh
Texte intégral:
Acta Pharmaceutica Sinica
Année:
2011
Type:
Article