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黄芪多糖联合顺铂对小鼠Lewis肺癌细胞肺转移的影响
Effects of Astragalus polysaccharide combined with cis-dichlorodiamineplatinumⅡ dichloridle on Lewis lung transplanted tumor metastasis and its mechanism
目的 观察黄芪多糖（APS）联合顺铂（DDP）对小鼠Lewis肺癌细胞肺转移、核因子（NF)-κB、P38、P53及Caspase-9表达的影响。方法 将90只Lewis小鼠随机分为模型组、顺铂组（6mg/kg DDP）、APS组（50、100、200）mg/kg，联合用药组［1/2 DDP+APS，即：（3+25、3+50、3+100）mg/kg］。各组均于造模第2天起用药，APS每日1次，DDP每周1次，连续20d。观察肿瘤肺转移情况，采用Real-time PCR法和Western blotting法检测肿瘤组织中NF-κB、P38、P65蛋白和基因，并用免疫组织化学检测Caspase-9的表达。 结果 与模型组相比，各治疗组均可降低肺转移灶数目（P<0.05或P<0.01）；除P38外，APS中、高剂量组可使小鼠Lewis肺癌组织中NF-κB p65、P53表达降低，Caspase-9表达增高；联合用药高剂量组作用则接近DDP组。结论 APS可抑制小鼠Lewis肺癌细胞的转移，抑制NF-κB和丝裂原活化蛋白激酶（MAPK）信号通路的激活，这可能是其抑制肿瘤转移的机制之一；APS与减半剂量的DDP铂类化疗药物联合使用时，作用增强，APS对DDP有增效减毒作用。
Objective To observe the influence of Astragalus polysaccharide (APS) combined with cis-dichlorodiaimineplatinumⅡ dichloridle (DDP) on pulmonary metastasis，the expression of nuclear factor(NF)-κB, P38, P53 and Caspase-9 in Lewis lung cancer tissue of mice. Methods Ninety mice with Lewis lung cancer were randomly divided into model group, DDP group(6mg/kg DDP), APS group（50, 100, 200）mg/kg, combination group［1/2 DDP+APS, means: (3+25, 3+50, 3+100)mg/kg］. All groups were treated on day after the day of model establishment, DDP 1/week, for 20 weeks. The number of the metastasis was observed. The expression of NF-κB, P38, P65 mRNA and protein were detected by Real-time PCR and Western blotting, respectively.Caspase-9 was tested by immunohistochemistry. Results Compared with control subgroups, tumor bearing subgroups, DDP, APS and DDP combined with APS, significantly reduced the number of pulmonary metastasis（P<0.05 or P<0.01）. Besides P38, the medium and high dose group of the APS reduced the expression of NF-κB and P53 in Lewis lung cancer tissues of mice. However, the expression of Caspase- 9 was upregulated. Effect of combination in high dose group was close to DDP group. Conclusion APS and APS combined with DDP can inhibit the number of pulmonary metastasis，and the activation of signal transduction pathway of NF-κB and mitogen-activated protein kinase(MAPK), which may be one of the mechanisms of anti-cancer and anti-metastasis. The APS and APS combined with 1/2 DDP increase the effect of anti-cancer and anti-metastasis, indicating that APS has efficacy enhancing and toxicity reducing of DDP.
黄芪多糖 / Lewis肺癌细胞 / 肺转移 / 实时定量聚合酶链反应 / 免疫印迹法 / 小鼠
Astragalus polysaccharides / Lewis lung cancer cell / Pulmonary metastasis / Real-time PCR / Western blotting / Mouse
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