乳移平配伍肺经引经药桔梗抗乳腺癌肺转移作用及机制的实验研究

目的从CXCL12/CXCR4生物学轴及癌基因HER-2角度出发,探讨＂乳移平＂配伍肺经引经药＂桔梗＂对人乳腺癌MDA-MB-435HM肺转移模型的抑制作用及机制。方法建立人乳腺癌细胞株MDA-MB-435HM肺转移模型,随机分为乳移平组、乳移平配伍桔梗组、乳移平配伍川牛膝组、阿霉素组及对照组。给药期间测原位瘤长、短径。给药结束后称瘤重,计算瘤重抑制率;行原位瘤及肺组织病理并定量分析各组肺转移情况;原位杂交法测各组原位瘤及肺组织中CXCL12、CXCR4及HER-2mRNA的表达。结果乳移平、乳移平配伍桔梗和阿霉素组对MDA-MB-435HM荷瘤裸鼠原位瘤和肺转移的发生均有一定的抑制作用。与乳移平单方比,乳移平配伍桔梗后可进一步提高荷瘤裸鼠原位瘤抑制率3.79%以及降低肺转移发生率26.44%。与对照组比较,乳移平和乳移平配伍桔梗组均能下调原位瘤中CXCR4和肺组织中CXCL12的表达;与乳移平单方比,乳移平配伍桔梗后可进一步下调原位瘤中CXCL12和肺组织中HER-2的表达（P〈0.01,P〈0.05）。结论与乳移平单方比,乳移平配伍桔梗后可进一步抑制乳腺癌肺转移的发生、发展,其作用机制可能通过调节CXCL12/CXCR4生物学轴及癌基因HER-2实现。

Effect and mechanism of ＂Ruyiping Formula＂ plus Platycodon grandiflorum in treating lung metastasis of breast cancer

Objective To observe the effect and mechanism of ＂Ruyiping Formula＂ plus platycodon grandiflorum,an herb guiding others to the lungs,in the treatment of lung metastasis of breast cancer in nude mice.Methods MDA-MB-435HM breast cancer lung metastasis was established in nude mice and then randomized into 5 groups： Ruyiping,Ruyiping plus platycodon grandiflorum,Ruyiping plus radix cyathulae,control group and doxorubicin group.The long and short diameters of the tumor were measured during the administration;the tumor weight was weighed to calculate inhibition rate of tumor after treatment;the lung metastasis was assessed in lung tissues.mRNA expression of CXCL12,CXCR4 and HER-2 genes in tumor and lung tissue with in situ hybridization method.Results Ruyiping,Ruyiping plus platycodon grandiflorum and doxorubicin group showed some inhibition effects on tumor growth and lung metastasis in MDA-MB-435HM breast cancer metastatic lung model.Compared with Ruyiping group,Ruyiping plus platycodon grandiflorum group further improved the inhibiton rates of tumor weight（3.79%） and lung metastasis（26.44%）.ISH assay indicated that Ruyiping and Ruyiping plus platycodon grandiflorum groups both downregulated the CXCR4 mRNA expression in tumor and CXCL12 mRNA expression in lung tissue（compared with control group）;compared with Ruyiping,Ruyiping plus platycodon grandiflorum group could further downregulate the CXCL12 mRNA expression in tumor（P〈0.01） and HER-2 mRNA expression in lung tissue（P〈0.05）.Conclusion Compared with Ruyiping,Ruyiping plus platycodon grandiflorum can further inhibit the progression of lung metastasis via regulating CXCL12/CXCR4 biolgical axis and HER-2 oncogene.