大蒜素对神经母细胞瘤生长的抑制作用

Inhibition of Allicin on Growth of Neuroblastoma in Vitro and in Vivo

【目的】探讨大蒜素对神经母细胞瘤生长的影响及相关机制。【方法】MTT法测定不同浓度大蒜素对神经母细胞瘤细胞生长的影响;建立裸鼠人神经母细胞瘤皮下移植瘤模型24只(n=8),随机分为对照组、大蒜素Ⅰ组(1mg·kg-1·d-1)和大蒜素Ⅱ组(10mg·kg-1·d-1),观察其对肿瘤生长的影响,荧光定量PCR法测定大蒜素对裸鼠皮下移植瘤VEGF mRNA表达的影响;ELISA法测定裸鼠血浆VEGF浓度;免疫组化法观察肿瘤微血管密度。【结果】不同浓度的大蒜素均能抑制神经母细胞瘤细胞的生长,高浓度的大蒜素能直接杀死肿瘤细胞;大剂量和小剂量大蒜素对裸鼠神经母细胞瘤皮下移植瘤均有抑制作用。对照组、大蒜素Ⅰ组和Ⅱ组的肿瘤体积为(2143±127)mm3、(1041±89)mm3和(904±65)mm3(P<0.05);大蒜素能下调神经母细胞瘤VEGF mRNA转录,对照组、大蒜素Ⅰ组和Ⅱ组VEGF mRNA表达量分别为(8.4±0.8)、(6.1±0.7)和(5.1±0.5);大蒜素能够抑制肿瘤细胞VEGF的表达,对照组、大蒜素Ⅰ组和Ⅱ组裸鼠血VEGF浓度分别为(78±10)、(45±8)和(35±7)pg/mL;大蒜素可以减少神经母细胞瘤的微血管密度。【结论】大蒜素在体内和体外均可抑制神经母细胞瘤细胞的生长,其机制与大蒜素抑制肿瘤细胞增殖和下调神经母细胞瘤VEGF mRNA的转录和蛋白表达有关。

[Objective] To investigate the efficacy and the possible mechanism of neuroblastoma induced by allicin. [Methods] MTT assay was used to test the effect of allicin on the growth of human neuroblastoma cell lines SK-N-SH. Twenty four nude mice bearing subcutaneous xenograft human neuroblastoma （NB） were randomly divided into 3 groups： the control group, the alliein groulp I （alliein 1 mg/kg/d） and group Ⅱ （allicin 10 mg/kg/d）. The role of alliein on the growth of the tumor was evaluated after 4 weeks, including the tumor volume and weight. The expression of VEGF mRNA was detected by fluorescent quantitation ploymerase chain reaction （FQ-PCRi. The serum VEGF concentration was measured by ELISA. The expression of MVD was analyzed with immunocytochemistry. [Results] Allicin inhibited the growth of NB in vitro and in vivo. The volume of tumor： the control group （2143 ± 127） mm3, allicin group I （1041 ± 89） mm3 and allicin group Ⅱ （904 ± 65） mm3 （P 〈 0.05）. The expression of VEGFmRNA and serum VEGF concentration was inhibited significantly by alliein. The expression of VEGF mRNA in the control group, the allicin group I and allicin group II was （8.4 ± 0.8）, （6.1 ± 0.7）, and （5.1±0.5）（P 〈 0.05）. The serum VEGF concentration in the control group, the allicin group I and alliein group II, bwas （78 ± 10）, （45± 8） and （35 ± 7） pg/mL （P 〈 0.05）. Alliein inhibit the expression of MVD of NB （P 〈 0.05）. [Conclusion] Allicin can inhibit the growth of NB in vitro and in vivo, which may be caused by suppression the expression of VEGF and MVD.