川芎嗪联合顺铂对小鼠肿瘤血管生成的研究

Study of tetramethylpyrazine combined with cisplatin on tumor growth and angiogenesis of Lewis lung cancer mice

目的研究川芎嗪联合顺铂对小鼠Lewis肺癌血管内皮生长因子(VEGF)和半乳糖凝集素1(Galectin-1)表达的影响。方法建立小鼠Lewis肺腺癌移植瘤模型。按照体重将小鼠随机分为4组,每组10只:空白组(0.9%NaCl 0.2mL),川芎嗪组(100 mg·kg^(-1),0.2 mL),顺铂组(2 mg·kg^(-1),0.2 mL),联合组(川芎嗪+顺铂,剂量同上,0.2 mL),腹腔注射,每日1次,给药14 d后,处死小鼠,计算抑瘤率。用免疫组化法检测VEGF、Galectin-1的表达。结果川芎嗪组、顺铂组、联合组的抑瘤率分别为20.42%,34.65%,59.81%。VEGF和Galectin-1的表达:空白组、川芎嗪组、顺铂组、联合组分别为(62.41±8.83)×10~3,(27.84±2.25)×10~3,(28.67±2.33)×10~3,(23.52±2.76)×10~3;(25.96±3.50)×10~3,(20.29±2.85)×10~3,(19.11±2.42)×10~3,(15.15±2.43)×10~3。与空白组比较,3个给药组差异均有统计学意义(均P<0.01);与川芎嗪组和顺铂组比较,联合组差异均有统计学意义(P<0.05,P<0.01)。VEGF与Galectin-1的表达呈正相关性(r=0.638,P<0.05)。结论川芎嗪能够抑制Lewis肺癌移植瘤生长,与顺铂联用有协同抑制作用,其作用机制可能是通过抑制VEGF与Galectin-1表达来抑制肿瘤血管生成进而抑制肿瘤生长。

Objective To investigate the effect of tetramethylpyrazine in combination with cisplatin on the expression of vascular endothelial growth factor（ VEGF） and Galectin-1 on Lewis lung cancer in mice.Methods A transplanted tumor model of Lewis lung cancer was established. Fourty mouse were randomly divided into four groups（ n = 10） ：blank group（ 0. 9% NaCl,0. 2 mL）,tetramethylpyrazine group（ 100 mg·kg^（-1）,0. 2 mL）,cisplatin group（ 2 mg·kg^（-1）,0. 2 mL）,and united group（ the doses as above）. Different treatments were served for 14 days,then all of rats were put to death to calculate inhibitory rate. The expression of VEGF and Galectin-1 were decteted by immunohistochemistry. Results The growth inhibition rate（ GIR） in tetramethylpyrazine group,cisplatin group,and united group were 20. 42%,34. 65%,59. 81%. The expression of VEGF and Galectin-1： blank group,tetramethylpyrazine group,cisplatin group,and united group were（ 62. 41 ± 8. 83） ×10~3,（ 27. 84 ± 2. 25） ×10~3,（ 28. 67 ± 2. 33） ×10~3,（ 23. 52 ± 2. 76） ×10~3;（ 25. 96 ± 3. 50） ×10~3,（ 20. 29 ± 2. 85） ×10~3,（ 19. 11 ± 2. 42） ×10~3,（ 15. 15 ± 2. 43） ×10~3 respectively. Compared with blank group,thediffernces in the three drugs groups were significant（ all P〈 0. 01）. Compared with tetramethylpyrazine group the differnces in united group were significant（ all P〈 0. 01）. Compared with cisplatin group,the difference of Galectin-1 and VEGF in united group were significant（ P〈 0. 05,P〈 0. 01）. The expression of VEGF had positive correlation with Galectin-1（ r = 0. 638,P〈 0. 05）. Conclusion Tetramethylpyrazine can effectively inhibit the growth of lewis lung cancer transplanted tumor,which has synergetic effect when used in combination with cisplatin. The mechanism might be that it can inhibit tumor angiogenesis by reducing VEGF and Galectin-1 expression.