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01.04.2010 | Original Article—Liver, Pancreas, and Biliary Tract

Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats

verfasst von: Hitoshi Yoshiji, Ryuichi Noguchi, Kosuke Kaji, Yasuhide Ikenaka, Yusaku Shirai, Tadashi Namisaki, Mitsuteru Kitade, Tatsuhiro Tsujimoto, Hideto Kawaratani, Hiroshi Fukui

Erschienen in: Journal of Gastroenterology | Ausgabe 4/2010

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Abstract

Background

Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Because neovascularization plays an important role in HCC, including hepatocarcinogenesis, an angiostatic therapy would be a promising approach for chemoprevention against HCC. The aim of the present study was to examine the combined effect of clinically used branched-chain amino acids (BCAAs) and an angiotensin-converting enzyme inhibitor (ACE-I), in conjunction with neovascularization, on hepatocarcinogenesis under the condition of IR.

Methods

The combined effect of the treatment on the development of liver enzyme-altered preneoplastic lesions, angiogenesis, and several indices was elucidated in obese diabetic rats. We also performed several sets of in vitro experiments to examine the mechanisms involved.

Results

When used individually, both BCAAs and ACE-I at clinically comparable low doses significantly attenuated the development of preneoplastic lesions, along with the suppression of both angiogenesis and vascular endothelial growth factor (VEGF) expression. The combination treatment with both agents exerted a more potent inhibitory effect than that of either single agent. Our in vitro study showed a similar combined effect on endothelial cell tubule formation.

Conclusion

This combination regimen showed a marked chemopreventive effect against hepatocarcinogenesis, along with suppression of neovascularization and VEGF expression, in obese diabetic rats. Because both BCAAs and ACE-Is are widely used in clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC in the future.

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Titel: Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats
verfasst von: Hitoshi Yoshiji
Ryuichi Noguchi
Kosuke Kaji
Yasuhide Ikenaka
Yusaku Shirai
Tadashi Namisaki
Mitsuteru Kitade
Tatsuhiro Tsujimoto
Hideto Kawaratani
Hiroshi Fukui
Publikationsdatum: 01.04.2010
Verlag: Springer Japan
Erschienen in: Journal of Gastroenterology / Ausgabe 4/2010
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-009-0158-z

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Background

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