【摘要】 目的观察丹参酮ⅡA在乳腺癌裸鼠模型体内的抗肿瘤作用,并初步探讨其机制。方法建立雌激素受体阳性细胞株MCF-7和雌激素受体阴性细胞株MDA-MB-231的裸鼠乳腺癌模型。分组分别以腹腔注射丹参酮ⅡA30 mg/kg 4周;他莫西芬灌胃1 mg/kg 4周和溶剂对照处理。取瘤体标本称重、流式细胞法分析肿瘤细胞凋亡情况、免疫组化法测量标本的p53、bcl-2、cerbB-2的表达并行半定量分析观察变化情况。结果在MCF-7组丹参酮ⅡA体积抑瘤率33.64%、瘤重抑瘤率32.24%;在MDA-MB-231组,丹参酮ⅡA体积抑瘤率达38.34%,瘤重抑瘤率39.82%,两种模型与他莫西芬组和溶剂对照组比较,差异均具有统计学意义(P<0.05)。流式细胞分析显示,丹参酮ⅡA在两种模型中均可上调肿瘤细胞凋亡分数(MCF-7组48.31%±5.84%、MDA-MB-231组50.25%±5.03%),较对照组及他莫西芬组差异均有统计学意义(P<0.05);免疫组化结果显示,在两种细胞株瘤体中,丹参酮ⅡA组与溶剂对照组比较,p53和bcl-2表达下调(P<0.05),cerbB-2的表达强度未见明显差异(P>0.05)。结论丹参酮ⅡA在乳腺癌MCF-7和MDA-MB-231细胞株裸鼠模型体内有明显的抑制肿瘤生长作用,且作用强于他莫西芬。其机制可能与诱导凋亡、下调bcl-2和p53的表达水平有关,而与cerbB-2的表达水平无关。更多还原

【Abstract】 Objective To confirm Tanshinone ⅡA’s(TanⅡA) anti-cancer activity on nude mice bearing human breast cancer cells with estrogen receptor(ER) positive and negative and to elucidate the mechanism of its activity in vivo.Methods Established the animal model of nude mices bearing human breast cell,both ER positive MCF-7 and ER negative MDA-MB-231,each group was divided into 3 subgroups,respectively by intraperitoneal injection of TanⅡA at a dose of 30 mg/kg 4 times/week,by gavage of Tamoxifen at a dose of 1 mg/kg 7 times/week and by solvent control for 4 weeks.All animals were tested for anti-cancer activity including the weights and the volumes of the tumor,apoptosis index by flow cytometry and expression of p53,bcl-2,cerbB-2 by immunohistochemistry method after the treatment.Results In MCF-7 group,there were a 33.64% tumor mass volume reduction and a 32.24% tumor mass weight reduction after TanⅡA treatment;in MDA-MB-231 group,a 38.34% tumor mass volume reduction and a 39.82% tumor mass weight reduction were observed in TanⅡA subgroups;the differences between TanⅡA and Tamoxifen or solvent control were statistically significant in both groups(P<0.05);Increase of apoptosic fiction by flow cytometry examination in TanⅡA subgroups in both MCF-7(48.31%±5.84%) and MDA-MB-231(50.25%±5.03%) groups were observed,there were both significant differences between TanⅡA and the other subgroups(P<0.05).Statistically significant decrease of p53 and bcl-2 expression were observed in TanⅡA between solvent control subgroup in both MCF-7 and MDA-MB-231 groups(P<0.05) while cerbB-2 had no significant difference with control group(P>0.05).Conclusion TanⅡA can inhibit both breast cancer cell MCF-7 and MDA-MB-231 growth in vivo,which had better anti-cancer effect than Tamoxifen.The mechanism may be associated with the induction of apoptosis,down regulation of the expression level of gene bcl-2 and p53,but may not with the expression level of cerbB-2.更多还原