Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58
| Autor: | Ya-Qi Deng, Feng-Yun Hu, Aiping Tong, Li Yang, Wen-Jun Huang, Xiao-Rong Zeng, Zhi-Yun Guo, Lei Li, Jinliang Yang, Rui Zhou |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Thienopyridine Pyridines Cell HSP27 Heat-Shock Proteins Mice Nude Antineoplastic Agents Apoptosis Thiophenes Pharmacology Biology Mice Aurora kinase medicine Animals Humans Electrophoresis Gel Two-Dimensional Transcription factor Heat-Shock Proteins Cell Proliferation Liver Neoplasms Hep G2 Cells General Medicine Cell cycle G1 Phase Cell Cycle Checkpoints Xenograft Model Antitumor Assays Molecular medicine digestive system diseases In vitro Tumor Burden Gene Expression Regulation Neoplastic medicine.anatomical_structure Oncology Cancer research Gene chip analysis Female Molecular Chaperones Transcription Factors |
| Zdroj: | Oncology Reports. |
| ISSN: | 1791-2431 1021-335X |
| DOI: | 10.3892/or.2012.1776 |
| Popis: | Despite progress made in the treatment of hepatocellular carcinoma (HCC), there is no curable treatment. Novel therapies are therefore needed. In our previous study on the design and synthesis of a small molecular inhibitor targeting Aurora kinase, we discovered a novel thienopyridine derivative compound (1g, TP58) which displayed the most potent and relatively specific inhibition of the proliferation of HepG2 human hepatoma cells in vitro. However, the molecular mechanism remains to be elucidated. Herein, in vitro and in vivo studies were conducted to further verify its antitumor activity against HCC. cDNA microarray and two-dimensional protein gel electrophoresis technology were utilized to elucidate the mechanism of HCC-specific inhibition of TP58. Flow cytometry analysis displayed that TP58 can significantly induce G0/G1 arrest in HepG2 cells. Sixteen genes involved in cell cycle regulation were found to be dysregulated following TP58 treatment using microarray technology. Nine proteins whose expression was altered (corresponding to 10 spots identified as differentially expressed) were identified by proteomic analysis. Further study showed that TP58 can modulate the expression of some liver-enriched transcription factors (LETFs) and liver-specific marker genes, such as hepatic nuclear factor (HNF-4) and α-fetoprotein (AFP). These findings may help explain the mechanism of HCC-specific antitumor activity of TP58 and provide some useful insight for anti-HCC drug design and future use of thienopyridine derivatives in HCC therapy. |
| Databáze: | OpenAIRE |
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