Total alkaloids of Rubus aleaefolius Poir. inhibit the STAT3 signaling pathway leading to suppression of proliferation and cell cycle arrest in a mouse model of hepatocellular carcinoma

Zhao,Jinyan; Lin,Wei; Cao,Zhiyun; Liu,Liya; Zhuang,Qunchuan; Zhong,Xiaoyong; Hong,Zhenfeng; Peng,Jun

doi:10.3892/or.2013.2585

September 2013 Volume 30 Issue 3

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September 2013 Volume 30 Issue 3

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Article

Total alkaloids of Rubus aleaefolius Poir. inhibit the STAT3 signaling pathway leading to suppression of proliferation and cell cycle arrest in a mouse model of hepatocellular carcinoma

Authors:
- Jinyan Zhao
- Wei Lin
- Zhiyun Cao
- Liya Liu
- Qunchuan Zhuang
- Xiaoyong Zhong
- Zhenfeng Hong
- Jun Peng
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Affiliations: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China
Pages: 1309-1314
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Published online on: July 3, 2013

https://doi.org/10.3892/or.2013.2585
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Abstract

Signal transducer and activator of transcription 3 (STAT3) plays a critical role in cell survival and proliferation and is constitutively activated in many types of human cancers including hepatocellular carcinoma (HCC). Therefore, it is a major focus in the development of anticancer agents. Rubus aleaefolius Poir. has been demonstrated to be effective in the treatment of HCC. However, the precise mechanism of its anticancer activity remains largely unknown. Using HepG2 cells and a HCC mouse xenograft model, in the present study we evaluated the effect of the total alkaloids of Rubus aleaefolius Poir. (TARAP) on tumor growth in vitro and in vivo and investigated the underlying molecular mechanisms. We found that TARAP inhibited the proliferation of HepG2 human HCC cells and blocked G1/S cell cycle progression. In addition, TARAP treatment suppressed STAT3 phosphorylation in tumor tissues. Consequently, the inhibitory effect of TARAP on STAT3 activation resulted in the inhibition of proliferation. Moreover, TARAP altered the expression of several important target genes of the STAT3 signaling pathway, such as decreased expression of cyclinD1, cyclinE, cyclin-dependent kinase (CDK) 4 and CDK2 as well as upregulated p21. These results suggest that suppression of the STAT3 signaling pathway leading to inhibition of proliferation and cell cycle arrest may be one of the mechanisms of the anticancer activity of TARAP against HCC.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Total alkaloids of Rubus aleaefolius Poir. inhibit the STAT3 signaling pathway leading to suppression of proliferation and cell cycle arrest in a mouse model of hepatocellular carcinoma

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