不同归经益药对骨转移癌CXCR4表达的影响

【作者】 林荔钦； 朱世杰；

【机构】 中日友好医院中西医结合肿瘤内科；

【摘要】 目的:观察不同归经补益类中药方剂在治疗骨转移癌的疗效差异,从CXCR4表达抑制情况分析其机理,为中药归经理论的临床应用提供实验依据。方法:本项研究采用转移性大鼠乳腺癌(MRMT-1)细胞,按Medhurst方法复制骨转移癌模型,分别观察不同归经补益类方药的作用。分别通过影像学方法进行评分、测量肿瘤体积,通过HE染色观察形态,用免疫组化法检测骨趋化因子受体4(CXCR4)表达并进行半定量分析。结果:本项研究所采用的骨转移癌模型,出现骨质破坏和肿瘤生长等表现。相对于假手术组,模型组影像学显示骨质破坏和肿瘤增长明显,CXCR4表达升高(P<0.01)。与模型组比较,肾经组影像学评分明显改善(P<0.05),CXCR4表达明显下降(P<0.01)。而肺经组和肝经组上述指标较模型组无统计学差异。结论:归肾经药物对骨转移癌灶的生长具有一定的抑制作用,其机制可能通过阻断SDF-1/CXCR4生物学轴及下游信号通路,从而达到抗肿瘤定向侵袭和增殖的目的。归肺经、归肝经药物不存在类似的作用,进而证实不同归经中药对机体的作用存在靶向特异性。更多还原

【Abstract】 Objective:The study was aimed to access and compare the efficacy of different channel tropism tonic formulas in rats with bone metastasis,investigate the theory of channel tropism based on the role of the SDF-1/CXCR4 axis,then provide a reliable experiment basis for its clinical application.Methods:A rat model of bone metastasis,using the MRMT-1 cell line injected into the tibia,was established according to the Medhurst Method to investigate the efficacy of different channel tropism tonic formulas.A series of experimental methods were adopted.Imaging methods were applied to score and measure the tumor volume,Volume of the bone tumor and structural damage to the bone weremeasured and graded byimaging methods,and morphological changes were investigated by HE staining.In addition,immunohistochemistry was selected to semi-quantitatively measure expressions of CXC chemokine receptors(CXCR4).Results:In this study,model groupsufferedobvious tumor growth and’severe bone destruction,with an obvious increase in CXCR4 expression(P < 0.01).Compared with model group,the radiological score of kidney channel group was improved significantly(P<0.05) in accompany with a conspicuous reduction in CXCR4 expression(P<0.01).Unlike kidney channel group,there was no significant difference for the above parameters between lung channel or liver channel group and model group.Conclusion:The results suggested that there were certain inhibitive effects of kidney channel formula onthe development of bone metastases,and it was probably relevant with the interruption of the SDF-1/CXCR4 axis and signaling pathways downstream from it,so as to resist proliferation and invasiveness of the tumors.As for lung channel formula and liver channel formula,both of them failed to work,which further confirmed that the effects of different channel tropism formulas have targeting specificity.更多还原