Tetramethylpyrazine-mediated suppression of C6 gliomas involves inhibition             of chemokine receptor CXCR4 expression.
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.
State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou 510060, PR China.
Keming
K
Yu
Zhao
Z
Chen
Xueke
X
Pan
Ying
Y
Yang
Sijia
S
Tian
Jing
J
Zhang
Jian
J
Ge
Bala
B
Ambati
Jing
J
Zhuang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D012074:Remission Induction; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C486264:Cxcr4 protein, rat; D011719:Pyrazines; D019718:Receptors, CXCR4; C017953:tetramethylpyrazine