Oncotarget

Research Papers:

Resveratrol inhibits age-dependent spontaneous tumorigenesis by SIRT1-mediated post-translational modulations in the annual fish Nothobranchius guentheri

Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie and Guorong Li _

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Oncotarget. 2017; 8:55422-55434. https://doi.org/10.18632/oncotarget.19268

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Abstract

Tingting Liu1, Long Ma1, Zhaodi Zheng1, Fenglin Li1, Shan Liu1, Yingbo Xie1 and Guorong Li1

1Shandong Provincial Key Laboratory of Animal Resistance Biology, School of Life Sciences, Shandong Normal University, Jinan, China

Correspondence to:

Guorong Li, email: [email protected]

Keywords: spontaneous tumorigenesis, resveratrol, SIRT1, post-translational modulations, annual fish

Received: March 01, 2017     Accepted: June 20, 2017     Published: July 15, 2017

ABSTRACT

Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls. Treated fish were fed with resveratrol (25 μg/fish/day) from sexual maturity (4-month-old) until they were sacrificed at 6-, 9- and 12-month-old. Immunoblot, immunohistochemistry and co-immunoprecipitation were employed to investigate the underlying mechanisms that resveratrol inhibited age-dependent spontaneous tumorigenesis in the fish. Results showed that resveratrol increased protein level of SIRT1 and alleviated age-associated tumorigenesis in liver. With SIRT1 up-regulation, resveratrol reduced proliferation by deacetylating K-Ras and inactivating K-Ras/PI3K/AKT pathway; and promoted apoptosis through deacetylation and dephosphorylation of FoxOs, up-regulation of DLC1 and interaction between SIRT1 and DLC1, and dephosphorylation of DLC1 in spontaneous neoplasms. We established a novel short-lived fish model for understanding the molecular mechanisms of drugs on age-dependent spontaneous tumorigenesis.


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