2-甲氧基雌二醇联合环磷酰胺对小鼠晚期乳腺癌模型的抑瘤作用

Antitumor Efficacy of 2-Methoxyestradiol plus Cyclophosphamide in Mice with Advanced Breast Cancer

目的:研究2-甲氧基雌二醇(2-ME2)和环磷酰胺(CTX)对小鼠晚期乳腺癌模型的抑瘤作用及两者结合的疗效。方法:将BALB/c 4T1乳腺癌模型小鼠,随机分为生理盐水对照组、2-ME2组、CTX组、2-ME2+CTX联合组,观察肿瘤生长情况;给药21 d后,处死小鼠并分离瘤组织和双肺,计算抑瘤率和肺转移率;免疫组化SP法检测瘤组织中缺氧诱导因子(HIF-1α)、血管内皮生长因子(VEGF)蛋白表达以及微血管密度(MVD)。结果:2-ME2+CTX联合组的抑瘤率高于2-ME2组、CTX组,差异有统计学意义(P<0.05);2-ME2+CTX联合组小鼠肺脏转移灶数目明显低于2-ME2组及CTX组,差异有统计学意义(P<0.05);2-ME2+CTX联合组移植瘤MVD及HIF-1α、VEGF蛋白表达明显低于2-ME2组和CTX组(P<0.05)。结论:2-ME2联合CTX应用对小鼠乳腺癌的疗效优于单用CTX或2-ME2;在抑制小鼠乳腺癌移植瘤血管新生方面,2-ME2、CTX具有协同作用。

OBJECTIVE：To study the antitumor efficacy of 2-methoxyestradiol （2-ME2） and cyclophosphamide （CTX） either alone or in combination in mice with advanced breast cancer.METHODS：BALB/c4T1 mice with breast cancer were randomly divided into control group,2-ME2 group,CTX group and 2-ME2＋CTX group,with tumor growth followed.After treatment of 3 weeks,the mice were sacrificed for isolation of tumor tissues and bilateral lungs with tumor inhibition rate and lung metastasis rate calculated; immunohistochemical SP method was applied for measurement of hypoxia-inducible factor （HIF-1 α）,protein expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） in tumor tissue.RESULTS：The tumor inhibition rate in 2-ME2 ＋ CTX group was higher than in 2-ME2 group or CTX group,and the differences were statistically significant （P〈0.05） ; the number of lung metastases was significantly lower in the 2-ME2 ＋ CTX group than in 2-ME2 group or CTX group,and the differences were statistically significant （P〈 0.05）; moreover,MVD,HIF-1α and VEGF protein expression of the transplanted tumor in 2-ME2 ＋ CTX group were significantly lower than in 2-ME2 group or CTX group （P〈0.05）.CONCLUSIONS：2-ME2 ＋ CTX is more effective than CTX or 2-ME2 alone against breast cancer in mice; 2-ME2 and CTX have synergistic inhibitory effect on neovasculization of transplanted tumor of breast cancer.