Genistein对乳腺癌细胞致成骨细胞生物学功能改变的影响  

Effects of Genistein on changes of osteoblastic biological function induced by breast cancer cells

作　　者：张燕燕[1] 朱国英[1] 顾淑珠[1] 陈晓[1] 

机构地区：[1]复旦大学放射医学研究所环境流行病与骨毒理研究室

出　　处：《中国骨质疏松杂志》2009年第7期506-512,共7页Chinese Journal of Osteoporosis

基　　金：上海市科委科研计划项目(064119512)

摘　　要：目的探讨Genistein对乳腺癌细胞致成骨细胞（osteoblast,OB）增殖、分化和矿化功能的影响,观察Genistein在乳腺癌骨转移的病理条件下是否能调节OB生物学功能。方法源于大鼠颅盖骨的原代OB与50%来自人源性乳腺癌细胞系MDA-MB-231或MCF-7的条件培养基（conditioned medium,CM）共同培养,并加入5×10-7mol/L（G7）、5×10-8mol/L（G8）或5×10-9mol/L（G9）的Genistein进行干预。MTT法观察其对OB增殖的影响;PNPP偶氮法观察其对OB碱性磷酸酶（alkaline phosphatase,ALP）活性的影响;茜素红S（ARS）进行矿化结节染色并计算面积以观察其对OB矿化能力的影响。结果MDA-MB-231和MCF-7细胞条件培养基可显著抑制OB的增殖。用Genistein干预1 d、3 d和5 d后,OB增值率可有不同程度的提高,差异有统计学意义（P〈0.05）。此外,乳腺癌细胞条件培养基可明显下调OB的ALP活性,而用不同浓度的Genistein干预后,OB的ALP活性分别较MDA-MB-231和MCF-7细胞条件培养基组增加22.7%、32.4%、63.5%和27.7%、32.0%、58.3%（P〈0.05）。Genistein还可改善乳腺癌细胞条件培养基对OB矿化能力的抑制,增加OB形成的矿化结节面积。结论在乳腺癌骨转移的病理条件下,Genistein可促进OB的增殖、分化和矿化能力,改善乳腺癌细胞对OB生物学功能的抑制作用。Objective To investigate the effects of Genistein on changes of osteoblastic proliferation, differentiation and mineralization induced by breast cancer ceils, and in order to observe whether Genistein regulates osteoblastic biological function in pathological condition with bone metastasis. Methods The osteoblasts harvested from calvaria of Sprague Dawley rats were cultured with 50% conditioned medium collected from two types of human breast cancer lines： MDA-MB-231 and MCF-7, and treated with different concentrations of Genistein ： 5 × 10^- 7 mol/L （ G7 ） ,5× 10^-8 mol/L （ G8）, 5 × 10^-9 mol/L （ Gg）. Then the proliferation was analyzed by MTT method, the alkaline phosphatase （ALP） activity was assessed by the p-nitrephenyl phosphate （PNPP） method, and the area of bone nodule formation was observed by alizarin red S （ARS） staining and measured to analyze the mineralization ability. Results Conditioned medium from MDA-MB-231 or MCF-7 significantly suppressed osteoblastic proliferation, while the proliferation on day 1, day 3 and day 5 was improved in the different extents when osteoblasts were treated with Genistein. Otherwise, conditioned medium significantly inhibited ALP activity on day 3, while compared with conditioned medium group, different concentrations of Genistein could increase the ALP activity of osteoblasts by 22.7 %, 32.4 % ,63.5 % and 27.7 %, 32.0 % ,58.3 %,respectively. Genistein also increased the area of bone nodule formation and improved osteoblastic mineralization ability inhibited by conditioned medium. Conclusion In pathological condition with bone metastasis, Genistein could promoto osteoblastie proliferation, differentiation and mineralization, improve osteoblastic biological function inhibited by breast cancer cells.

关 键 词：GENISTEIN 乳腺癌细胞 成骨细胞 增殖 分化 矿化结节 

分 类 号：R73-3[医药卫生—肿瘤]