Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti-apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In Vivo.

Abstract:

BACKGROUND/AIM:In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS:HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. RESULTS:Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION:Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Tsai JJ,Hsu FT,Pan PJ,Chen CW,Kuo YC

doi

10.21873/anticanres.12452

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

2119-2125

issue

4

eissn

0250-7005

issn

1791-7530

pii

38/4/2119

journal_volume

38

pub_type

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