麦角甾醇对S180荷瘤小鼠肿瘤血管生成和Bax、Bcl-2表达的影响

EFFECTS OF ERGOSTEROL IN TUMOUR ANGIOGENESIS AND EXPRESSION OF BAX AND BCL-2 IN S180 TUMOR-BEARING MICE

目的探讨麦角甾醇对S180荷瘤小鼠肿瘤血管和Bax、Bcl-2蛋白的影响。方法建立S180荷瘤小鼠模型,将50只荷瘤小鼠随机等量分为模型对照组、环磷酰胺组(CTX),麦角甾醇高、中、低剂量组,雌雄各半,连续给药21d天后颈椎脱臼处死。计算胸腺指数、脾脏指数和抑瘤率;硝酸还原酶法测定肝脏中一氧化氮(NO)含量;酶联免疫吸附试验(ELISA)测定肿瘤组织中小鼠血管内皮生长因子A(VEGF-A)含量;免疫组织化学法检测肿瘤组织中Bax、Bcl-2蛋白的表达。结果与模型对照组相比,环磷酰胺组、高、中、低剂量组抑瘤率分别是53.96%、41.64%、29.90%、19.52%,均有显著性差异(P<0.05),高、中、低剂量组胸腺指数、脾脏指数均明显增大(P<0.05);与模型对照组相比,实验组(高、中、低剂量组)中NO含量和小鼠血管内皮生长因子A(VEGF-A)表达水平明显降低(P<0.05),且均能明显下调Bcl-2表达水平(P<0.05),明显上调Bax表达水平(P<0.05),Bax/Bcl-2比例明显增大(P<0.05)。与环磷酰胺组相比,实验组NO含量和VEGF-A水平、Bcl-2、Bax表达水平均有统计学差异(P<0.05)。结论香菇提取物麦角甾醇具有抑瘤作用,且与剂量有关,其可能抗肿瘤机制是抑制肿瘤血管生成和调控Bax、Bcl-2蛋白表达水平。

Objective To investigate the effects of ergosterol on blood vessels of tumour tissues and expression of Bax and Bcl-2 in S180 tumor-bearing mice. Methods Fifty S180 tumor-bearing mice were randomly divided into five groups of equal size, including model group, cytoxan （CTX） group, high, middle, low dose of ergosterol groups with equal number of male and female mice in each group. Ergosterol was given successively for 21 days, and then the mice were sacrificed. Spleen and thymus indexes and tumor inhibitory rate were calculated. The content of NO was evaluated by nitrale reduetase （NR） assay. The level of vascular endothelial growth factor A （VEGF-A） was measured by ELISA. Immunohistochemistry（IHC） was used to determine the expression level of B-cell lymphoma 2-like protein 4 （Bax） and B-cell lymphoma 2 （Bcl-2）. Results Compared with the model group, the tumor inhibitory rates in CTX, ergosterol high, middle and low dose groups were 53.96%, 41.64%, 29.90%and 19.52% respectively（P〈0.05）. The spleen and thymus indexes were increased significantly （P〈0.05） in ergosterol high, middle and low dose groups than those in model group. Compared with the model group, all three ergosterol groups showed that the content of NO and the level of VEGF-A were significantly decreased （P〈0.05） and the expression level of Bcl-2 was decreased but Bax was increased significantly （P〈0.05）. Compared with the CTX group, the expression level of NO, VEGF-A, Bcl-2 and Bax were significant different （P〈0.05）. Conclusion Ergosterol exhibited antitumor activity in a dose-dependent manner. The potential mechanisms may be associated with inhibiting tumor angiogenesis and regulating the expression level of Bax and Bcl-2.