原创力文档n-acetylcysteine improves antitumoural response of interferon alpha by nf-kb downregulation in liver cancer cells干扰素α的防治作用改善antitumoural响应的差别nf-kb对这些肝癌细胞.pdfVIP
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n-acetylcysteine improves antitumoural response of interferon alpha by nf-kb downregulation in liver cancer cells干扰素α的防治作用改善antitumoural响应的差别nf-kb对这些肝癌细胞
Kretzmann et al. Comparative Hepatology 2012, 11:4
/content/11/1/4
RESEARCH Open Access
N-acetylcysteine improves antitumoural response
of Interferon alpha by NF-kB downregulation in
liver cancer cells
1,2* 3 2 2 1
Nelson Alexandre Kretzmann , Eduardo Chiela , Ursula Matte , Norma Marroni and Claudio Augusto Marroni
Abstract
Background: Liver cancer is one of the most common malignancies in the world and at the moment, there is no
drug intervention effective for the treatment of liver tumours. Investigate the effect of N-acetylcysteine (NAC),
which has been studied for its antitumoural properties, on the toxicity of hepatocarcinoma (HCC) cells in vitro when
used with the drug interferon alpha-2A (IFN), which is used clinically to treat HCC.
Results: NAC, IFN and NAC plus IFN reduced cell viability, as determined by MTT assay. More importantly, NAC
potentiates the cytotoxic effect of IFN, with the best response achieved with 10 mM of NAC and 2.5 x 104 of IFN.
These results were confirmed by Annexin/PI staining through flow cytometry and morphologic analyses.
Co-treatment reduced the expression of the nuclear transcription factor kappa-B (NF-kB). In a similar way to NAC,
RNAi against p65 potentiated the toxic effect of IFN, suggesting that, indeed, NAC may be enhancing the effect of
IFN through inhibition of NF-kB.
Conclusions: Our results support the notion that NAC may be an important drug for the treatment of liver
tumours as primary or adjuvant therapy. IFN has a limited clinical response, and therefore, the anti-proliferative
properties of NAC in the liver should be explored further as an alternative for non-responders to IFN treatment.
Keywords:
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