氧化苦参碱对B16-BL6细胞转移作用的影响

Influence of oxymatrine on anti-cell metastasis of line B16-BL6

目的探讨氧化苦参碱抗肿瘤转移的作用及其作用机制。方法在黑色素瘤细胞(B16-BL6细胞株)培养液中加入梯度浓度(0、1、10、20、50、100μmol/L)的氧化苦参碱,并采用MTT法检测肿瘤细胞增殖抑制率。采用静脉注射方法建立肿瘤转移小鼠模型,以低剂量和高剂量(20 mg/kg,40 mg/kg)两个剂量组灌胃治疗,23 d后解剖小鼠对肺部转移灶计数观察。并取定量肺组织,取匀浆。以ELISA法检测金属蛋白酶MMP-2,MMP-9的含量。结果在体外实验中氧化苦参碱可抑制黑色素瘤细胞的增殖,并存在量效关系。IC50值为38.6μmol/L。动物实验中低剂量和高剂量组肺部转移灶都比模型组少,并有显著差异(P<0.05或P<0.01)。低剂量和高剂量组的肺组织的MMP-2,MMP-9的表达量均减少,与模型组比较有显著差异(P<0.05或P<0.01)。结论氧化苦参碱对肿瘤细胞有抑制作用,并可抗肿瘤转移,其作用部分机制可能与抑制金属蛋白酶MMP-2,MMP-9表达有关。

Objective To explore the effect of oxymatrine on anti-tumor metastasis of line B16-BL6 and its related mechanism.Methods Adding oxymatrine of gradient concentrations（ 0,1,10,20,50,100 μmol / L） into the melanoma cell-culture medium,then the inhibition rate of tumor cell proliferation was detected by MTT.Mice model was treated by intravenous injection,then the mice was treated with gavage therapy in two dosage groups,a low dosage group（ 20 mg / kg） and a high dosage group（ 40 mg / kg）.After 23 days,the mice were dissected to count and observe the lung metastases.The content of metalloproteinase,MMP-2 and MMP-9 were measured by ELISA.Results In vitro experiments,oxymatrine inhibited the proliferation of melanoma cells,and there was a dose-effect relationship.The IC50 value was 38.6 μmol / L.In animal experiments,lung metastases in both low and high dosage groups were less than those in the model group,and there was a significant difference（ P〈0.05 or P〈0.01）.The expression index of MMP-2 and MMP-9 in the lung tissue of both the low and the high dosage groups decreased.Compared with the model group,there was a significant difference（ P 〈0.05 or P〈0.01）.Conclusion Oxymatrine has a inhibitory effect on tumor cells and the anti-tumor metastasis effect.The mechanism of its action may partly be in relation to the inhibition of the expression of MMP-2 and MMP-9.