摘要
背景与目的:在肿瘤的发生、发展中,环氧合酶(cyclooxygenase,COX)起了很重要的作用,而多种COX抑制剂可以抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡。本实验观察不同浓度赖氨匹林(Aspisol)对小鼠移植性乳腺癌的抑制作用以及对肿瘤细胞凋亡和对肿瘤组织环氧合酶-2(COX-2)、Caspase-3蛋白的表达的影响,并探讨其抑制乳腺癌生长的作用机制。方法:用细胞悬液法将肿瘤细胞接种于C3H小鼠前肢腋窝皮下,制备可移植肿瘤模型。次日给予不同浓度的Aspisol腹腔注射,每天一次,共28天,用氟尿嘧啶(5-fluorouracil,5-FU)和生理盐水分别作为阳性对照和阴性对照。计算Aspisol的抑瘤率;原位凋亡检测法(TUNEL)检测Aspisol对肿瘤细胞凋亡的影响;免疫组化法检测Aspisol对小鼠肿瘤组织的COX-2、Caspase-3表达的影响。结果:175、350、700mg/kgAspisol对小鼠乳腺癌的抑瘤率分别为38.9%、48.2%、47.0%,10mg/kg5-FU的抑瘤率为60.4%。各给药组肿瘤细胞均呈现明显凋亡形态改变,不同浓度Aspisol均明显下调小鼠肿瘤组织COX-2的表达,增强Caspase-3表达。结论:Aspisol对C3H小鼠移植性乳腺癌的生长具有抑制作用;能诱导肿瘤细胞的凋亡,其机制可能与抑制COX-2表达、增强Caspase-3表达有关。
BACKGROUND ＆ OBJECTIVE： Cyclooxygenase （COX） plays an important role in tumorigenesis and development. Many inhibitors of COX could inhibit proliferation and induce apoptosis of cancer cells. This study was to observe the inhibitory effect of Aspisol on growth of transplanted breast cancer in C3H mice and the effects of Aspisol on tumor cell apoptosis and the expression of Caspase-3 and COX-2, and explore the mechanisms. METHODS： The suspension of breast cancer cells was injected subcutaneously into forelimb axillas of C3H mice to establish xenograft models. From the next day, the mice received intraperitoneal injection of different concentrations of Aspisol once a day for 28 days;the mice received injection of 5-fluorouracil （5-FU） were used as positive controls, and the mice received injection of normal saline （NS） were used as negative controls. The inhibition rate of tumor growth was calculated. Tumor cell apoptosis was detected by TUNEL assay. The expression of Caspase-3 and COX-2 was detected by immunohistochemistry. RESULTS： The inhibition rate of tumor growth was 38.9% in 175 mg/kg Aspisol group, 48.2% in 350 mg/kg Aspisol group, 47.0% in 700 mg/kg Aspisol group, and 60.4% in 10 mg/kg 5-FU group. Typical apoptotic morphologic changes were seen in the 4 groups. Caspase-3 expression was significantly higher and COX-2 expression was significantly lower in Aspisol groups than in NS group. CONCLUSIONS： Aspisol may inhibit the growth of transplanted breast cancer in C3H mice, and induce tumor cell apoptosis. The mechanism may be correlated to downregulation of COX-2 and up-regulation of Caspase-3.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2006年第12期1497-1501,共5页
Chinese Journal of Cancer
基金
安徽省教育厅自然科学研究项目(No.2005KJ047ZD)~~
