中国中西医结合杂志2011,Vol.31Issue(5):684-689,6.
从OPG/RANKL/RANK系统阐述补骨脂-蛇床子抑制乳腺癌骨转移的机制
Inhibitory Acting Mechanism of Psoralen-Osthole on Bone Metastasis of Breast Cancer-An Expatiation Viewing from OPG/RANKL/RANK System
摘要
Abstract
Objective To find the optimal proportion of Composite Fructus Psoraleae and Fructus Cnidii (CFPC) for inhibiting the bone metastasis of breast cancer by way of exploring its acting mechanism viewing from OPG/RANKL/RANK system. Methods The human bone metastasis of breast cancer model was established by injecting tumor cells of MDA-MB-231 BO cell line into the left cardiac ventricle of nude mice. The modeled mice were randomly divided into seven groups: the blank group administered with normal saline by gastrogavage, the positive control group with zoledronic acid via peritoneal injection, and the 5 tested group with CFPC in different proportions of Fructus Psoraleae and Fructus Cnidii, i.e. ( A, 4:0; B, 3:1; C, 1: 1; D, 1: 3, and E 0: 4), given by gastric infusion. The treatment started from 1 week after modeling and lasted for six weeks. By the end of the experiment, the metastatic foci in bone were imaged by radionuclide tracing method and X-ray photograph, and separated for detecting gene and protein expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), interleukin-8 (IL-8), parathyroid hormone-related protein (PTHrP), macrophage colony stimulating factor (MCSF) by Real-time PCR and Westem blot respectively. Results Inhibition of bone metastasis gene was displayed to some extent in all the tested groups treated with CFPC, showing an increased level of OPG mRNA expression ( It was 60. 343 ±6.274 in the tested group C), and decreased mRNA expressions of IL-8, PTHrP, MCSF, RANKL (218.010 ± 12.802, 232.399 ± 14. 354, 319.831 ±5.322, and 195.701 ± 4. 862, respectively in the tested group C). The optimal effect was shown in the tested group C, showing significant difference to that in the blank group ( P<0. 01 ). Meanwhile, the OPG in the bone metastatic foci could be up-regulated and protein expressions of RANKL/IL-8/PTHrP/MCSF down-regulated in all the tested groups. The optimal effect was shown in the tested group C, with significant difference from those of the normal saline group.Conclusion CFPC could inhibit the bone metastasis of breast cancer through activating OPG/RANKL/RANK pathway. Among different proportions of Fructus Psoraleae and Fructus Cnidii, 1:1 was the best one.关键词
骨转移/动物模型/蛇床子/补骨脂Key words
bone metastasis/ animal model/ Fructus Psoraleae/ Fructus Cnidii引用本文复制引用
刘胜,吴春宇,程旭锋,杨顺芳,宋晓耘..从OPG/RANKL/RANK系统阐述补骨脂-蛇床子抑制乳腺癌骨转移的机制[J].中国中西医结合杂志,2011,31(5):684-689,6.基金项目
国家自然科学基金资助项目(No.30772811) (No.30772811)
上海市教委曙光跟踪计划资助项目(No.08GG12) (No.08GG12)
上海高校创新团队中医外科学资助项目 ()