蛇床子-补骨脂配伍引经药对乳腺癌骨转移裸鼠CXCL12-CXCR4轴的影响

Effects of Platycodonis Radix Combined with Cnidii Fructus-Psoraleae Fructus on CXCL12-CXCR4 Axis in Nude Mice with Bone Metastasis of Breast Cancer

目的:观察蛇床子-补骨脂配伍引经药桔梗对裸鼠乳腺癌骨转移趋化因子12-趋化因子受体4(CXCL12-CXCR4)生物轴的影响,并探讨其机制。方法:采用左心室注射乳腺癌MDA-MB-231BO细胞法建立乳腺癌骨转移裸鼠模型,分别ig"蛇床子(1.28 g)-补骨脂(1.28 g)"煎液、"蛇床子(1.28 g)-补骨脂(1.28 g)-桔梗(0.32 g)"煎液、"蛇床子(1.28 g)-补骨脂(1.28g)-牛膝(0.32 g)"煎液,观察其对裸鼠模型上肢和下肢骨转移损伤、骨转移程度的影响,逆转录-PCR(RT-PCR)和免疫印迹法(Western blot)检测上下肢骨转移灶中CXCL12,CXCR4 mRNA和蛋白的表达。结果:"蛇床子-补骨脂"对裸鼠上肢、下肢骨转移程度、骨损伤程度、骨转移组织中CXCL12和CXCR4 mRNA的表达均有一定的抑制作用(P<0.05),上行引经药桔梗可增强"蛇床子-补骨脂"对上肢骨转移程度、骨损伤程度、骨转移组织中CXCL12和CXCR4 mRNA和蛋白表达的抑制作用(P<0.05)。下行引经药牛膝对上述指标无明显影响。结论:桔梗可增强"蛇床子-补骨脂"对乳腺癌骨转移裸鼠上肢骨转移的治疗作用,其机制可能与其增强"蛇床子-补骨脂"下调上肢骨转移灶中CXCL12,CXCR4 mRNA和蛋白表达有关。

Objective： To observe the effects of Platycodonis Radix combined with Cnidii Fructus-Psoraleae Fructus on C-X-C chemokine ligand 12 （CXCL12）-C-X-C chemokine receptor 4 （CXCR4） axis in nude mice with bone metastasis of breast cancer. Method： The model of bone metastasis of breast cancer in nude mice were established by left ventricle injection of MDA-MB-231BO cells. The modeled mice were treated with traditional Chinese medicine decoction ‘Cnidii Fructus 1.28 g -Psoraleae Fructus 1.28 g’, ‘Cnidii Fructus 1.28 g-Psoraleae Fructus 1.28 g -Platycodonis Radix 0.32 g’ and ‘Cnidii Fructus 1.28 g-Psoraleae Fructus 1.28 g-Cyathulae Radix 0.32 g’. After the interventions, the nude mice models were observed for the effects of the treatment methods on upper limb and lower limb bone metastasis damages and degree of bone metastases, CXCL12 and CXCR4 mRNA expressions and protein expressions in bone metastasis lesions of upper and lower limbs were detected by RT-PCR and Western blot. Result： Cnidii Fructus-Psoraleae Fructus had certain inhibitory effects on bone metastasis degree, bone damage degree of upper limb and lower limb, as well as CXCL12 and CXCR4 gene expressions in bone metastases tissues （P〈0.05）. The upward medicinal guide drug Platycodonis Radix can enhance the inhibitory effect of Cnidii Fructus-Psoraleae Fructus on bone metastasis degree, bone damage degree of upper limb, as well as mRNA and protein expressions of CXCL12 and CXCR4 in bone metastasis tissues （P〈0.05）. The downward medicinal guide drug Achyranthes had no obvious effects on the above indexes. Conclusion： Platycodonis Radix can enhance the therapeutic effect of Cnidii Fructus-Psoraleae Fructuson in nude mice with bone metastasis of breast cancer, and the mechanism may be associated with the enhancing effect of Cnidii Fructus-Psoraleae Fructus on down-regulating the mRNA and protein expressions of CXCL12 and CXCR4 in bone metastasis lesions of upper limb.