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
| Autor: | Zhiyun Cao, Wei Lin, Qunchuan Zhuang, Liya Liu, Zhenfeng Hong, Jinyan Zhao, Xiaoyong Zhong, Jun Peng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
STAT3 Transcription Factor Cancer Research Carcinoma Hepatocellular Cell cycle checkpoint Blotting Western Cell Mice Nude Apoptosis Real-Time Polymerase Chain Reaction Plant Roots Stat3 Signaling Pathway Immunoenzyme Techniques Mice Alkaloids Cyclin-dependent kinase Tumor Cells Cultured medicine Animals Humans RNA Messenger Phosphorylation STAT3 Rosaceae Tumor Stem Cell Assay Cell Proliferation Mice Inbred BALB C biology Reverse Transcriptase Polymerase Chain Reaction Liver Neoplasms Cyclin-dependent kinase 2 Cell Cycle Checkpoints General Medicine Cell cycle Xenograft Model Antitumor Assays Cell biology medicine.anatomical_structure Oncology biology.protein STAT protein Signal Transduction |
| Zdroj: | Oncology Reports. 30:1309-1314 |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2013.2585 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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