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槲皮素联合川芎嗪对小鼠Lewis 肺癌生长的抑制作用

Inhibitory Effect of Quercetin in Combination with Tetramethylpyrazine on Growth of Lung Adenocarcinoma in Mice

  • 摘要: 目的 探讨槲皮素联合川芎嗪对小鼠Lewis肺癌生长的抑制作用及其机制。方法 复制C57BL小鼠Lewis肺癌模型,将40只接种Lewis肺癌的C57BL小鼠随机分成4组:对照组(A组)、槲皮素组(B组)、川芎嗪组(C组)、槲皮素+川芎嗪组(D组),每组10只。连续用药20日,观察移植瘤生长情况,于接种后第22天处死各组小鼠,采用免疫组化半定量检测肿瘤组织微血管密度(MVD)、血管内皮生长因子(VEGF)及增殖核抗原(PCNA)的表达水平,用原位凋亡TUNEL法检测肿瘤细胞凋亡指数(AI)。结果 (1)B、C、D组肿瘤的生长明显受到抑制,瘤重明显低于A组,其抑瘤率分剐为39.87%、35.45%、54.58%,D组抑瘤率明显高于B、C组,差异有显著性(P〈0.05)。(2)B、C、D组MVD、VEGF及PCNA表达水平明显低于A组(P〈0.05或0.01),尤其是D组表达最低。B、C、D组AI较A组增高(P〈0.05或0.01),D组最高。结论 槲皮素与川芎嗪联合用药可明显抑制Lewis肺癌移植瘤的生长,其作用机制与抑制微血管生成、抑制细胞增殖和促进细胞凋亡有关。

     

    Abstract: Objective  To explore the inhibitor effect and its mechanism of quercetin combination with tetramethylpyrazine on growth of lung carcinoma in mice. Methods  The Lewis lung carcinoma models of C57 BL mice were establish. Forty C57BL mice were randomly divided into 4 groups : control group ( Group A), quercetin group (Group B), tetramethylpyrazine group (Group C) and quercetin + tetramethylpyrazine group (Group D) .Different treatments were served from day 2 after transplantation and all mice were sacrificed after 22 days. The volumes of tumors were measure respectively during the therapy time ; subcutaneous tumors were processed for histological examination. The expression of microvessel density (MVD), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were detected by immunhistochemical method. The apoptosis index (AI) was measured by biotinyated-dUTP nick and labeling ( TUNEL) . Results  (1) The tumor growth was suppressed significantly in Group B, C and D. The weights of tumor were markedly decreased in Group B, C and D compared with Group A. Group B, C, D had a growth inhibition rate of 39. 87 %,35. 45 % and 54. 58 % respectively. (2) The expression levels of VEGF, MVD and PCNA were significantly lower in Group B, C, D than group A. AI was enhanced in Group B, C, D, compared with Group A. Conclusion  Quercetin combination with tetramethylpyrazine can remarkably inhibit the growth of Lewis lung carcinoma in mice, and its mechanisms might be relative to inhibiting the angiogenesis and tumor proliferating and inducing apoptosis.

     

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