Tetramethylpyrazine-mediated suppression of C6 gliomas involves inhibition of chemokine receptor CXCR4 expression
| Autor: | B. K. Ambati, Keming Yu, Jing Zhang, Sijia Tian, Xueke Pan, Zhao Chen, Jian Ge, Ying Yang, Jing Zhuang |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Receptors CXCR4 Cell Survival Gene Expression Antineoplastic Agents Biology Rats Sprague-Dawley chemistry.chemical_compound Chemokine receptor In vivo Cell Movement Glioma Cell Line Tumor medicine Tetramethylpyrazine CXCL10 Animals Confluency Brain Neoplasms Remission Induction General Medicine medicine.disease Xenograft Model Antitumor Assays In vitro Rats Tumor Burden Oncology chemistry Cell culture Pyrazines Cancer research |
| Zdroj: | Oncology reports. 28(3) |
| ISSN: | 1791-2431 |
| Popis: | Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb Chuanxiong. Increasing numbers of studies have indicated that tetramethylpyrazine hydrochloride (TMPH) has anticancer effects. However, the molecular mechanisms underlying the actions of TMPH have not been fully elucidated. In this study, using real-time RT-PCR and western blot techniques, we demonstrate that TMPH significantly downregulates the expression of the chemokine receptor CXCR4 in C6 glioma cells. Consistent with a role for CXCR4 in cancer development, TMPH inhibits the migration, proliferation and colony formation of C6 glioma cells in vitro more effectively than the CXCR4 antagonist AMD3100. Interestingly, TMPH does not affect the cell cycle when the cells are grown to 50-80% confluency but induces S-phase arrest at 100% confluency, as indicated by a significant reduction in the G1 and G2 populations. These findings were also confirmed in vivo. Rats were implanted with C6 glioma cells and treated with 100 mg/kg TMPH for 20 days. Our data show that tumour growth was significantly inhibited in rats treated with TMPH (4.14±2.81 mm3) compared with tumour growth in control rats (55.9±14.12 mm3). Microcirculation in the implants was sparser in the TMPH-treated rats than that in the control rats, as measured by FITC-dextran staining. Consistent with the in vitro results, TMPH significantly downregulated the expression of CXCR4 in C6 glioma implantation compared with the control. This study provides new insights into the mechanisms of the TMPH anticancer effects. |
| Databáze: | OpenAIRE |
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