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《Chinese Journal of Pharmacology and Toxicology》 1993-02
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Antimetastatic action of tetramethylpyrazine and its mechanism

LIU Jin-Rong,YE Song-Bai(Department of Pharmcology,West China University of Medical Sciences,Chengdu 610041) Institute of Blood Transfusion,Chinese Academy of Medical Sciences. Chengdu 610081  
Tetramethylpyrazine(TTMP),one of the active ingredients isolated from Ligusticum wallichii Franch,has a conspicuous effect on hemodynamics and blood coagulation mechanism.A study has been made on the effect of TTMP on the ability of B16-F10 melanoma to metastasize in the syngenic C57BL/6J mice after injection of 106 viable B16 F10 melanoma cells.To clarify the mechanism further,a study was made on the effect of TTMP on the plasma concentration of TXA2 and PG12 in mice,on the NK activity in these mice and on the biosynthesis of DNA,RNA and protein in B16-F10 melanoma cells.The results showed that: 1.TTMP reduced the experimental pulmonary metastasis at a dose of 20 mg·kg-1·d-1 for 18 d.The pulmonary metastasis nodules were significantly decreased from 134 to 72 as compared with those in the control; 2.The plasma concentration of TXA2 of the B16 bearing mice was higher than that of normal mice.After the treatment with TTMP a decreased content of TXA2 was found without the change of the PGl2 level; 3.Augmentation ofthe NK cell activity of the splenocytes by TTMP was observed in vivo in the normal mice and B16 bearing mice.TTMP also antagonized the suppressing effect of cyclophosphamide on the murine NK cells; 4.TTMP at a large dose could inhibited DNA,RNA and protein biosynthesis in the B16 F10 melanoma cells and the effect was dose dependent.To sum up,these studies indicate that: 1.TTMP is effective in preventing the pulmonary metastasis of B16 F10 melanoma; 2.The antimetastatic action of TTMP may be related not only to lowering the effect on the level of TXA2,thereby decreasing the TXA2/PGI2 ratio,but also to promoting the effect on the NK cell activity.
【Key Words】： Tetramethylpyrazine Neoplasm metastasis Thromboxane B2 6 Keto PGF1αNatural killer cells
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