复方苦参注射液联合5-氟尿嘧啶节律化疗对人胃癌裸鼠移植瘤VEGF、CXCR4和SDF-1表达的影响

Effect of Fufang Kushen Injection Combined with Metronomic Chemotherapy of 5-Fluorouracil on Expressions of VEGF,CXCR4 and SDF-1 in Human Gastric Cancer Xenografts in Nude Mice

背景:前期研究证实复方苦参注射液联合5-氟尿嘧啶(5-Fu)节律化疗可抑制人胃癌裸鼠移植瘤生长,降低肿瘤组织微血管密度(MVD),但其具体机制尚未阐明。目的:研究复方苦参注射液联合5-Fu节律化疗对人胃癌裸鼠移植瘤血管内皮生长因子(VEGF)、CXC趋化因子受体4(CXCR4)和基质细胞衍生因子-1(SDF-1)表达的影响,以探讨两者联合抗肿瘤血管生成的可能机制。方法:建立人胃癌裸鼠移植瘤模型,随机分为对照组、5-Fu节律化疗组、复方苦参注射液组和联合治疗组(5-Fu+复方苦参注射液)。RT-PCR、免疫组化法检测移植瘤组织VEGF、CXCR4 mRNA和蛋白表达,ELISA法检测移植瘤、肝和肺组织SDF-1蛋白表达。结果:5-Fu节律化疗组、复方苦参注射液组和联合治疗组裸鼠移植瘤组织VEGF、CXCR4 mRNA和蛋白表达均较对照组显著下降,移植瘤、肝和肺组织SDF-1蛋白表达较对照组显著下降,且联合治疗组显著低于5-Fu节律化疗组和复方苦参注射液组(除肝组织SDF-1表达)。结论:复方苦参注射液联合5-Fu节律化疗可能通过协同抑制移植瘤组织的VEGF、CXCR4和SDF-1表达,以抑制肿瘤血管生成。

Background： Pilot studies have indicated that Fufang Kushen Injection combined with metronomic chemotherapy of 5-fluorouracil （5-Fu） can inhibit the growth and reduce microvessel density （MVD） of human gastric cancer xenografts in nude mice, but its mechanism has not been clarified~ Aims： To study the effect of Fufang Kushen Injection combined with metronomic chemotherapy of 5-Fu on the expressions of vascular endothelial growth factor （VEGF）, CXC chemokine receptor 4 （CXCR4） and stromal-derived factor-1 （SDF-1） in human gastric cancer xenografts in nude mice for clarifying their possible mechanism of anti-angiogenesis. Methods： Nude mice were randomized into control group, 5-Fu metronomic chemotherapy group, Fufang Kushen Injection group and combined treatment group （5-Fu metronomic chemotherapy combined with Fufang Kushen Injection） after establishing the human gastric cancer xenografts. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expressions of VEGF and CXCR4 in tumor tissue. ELISA was used to assess the protein expression of SDF-1 in tumor, liver and lung tissues. Results： mRNA and protein levels of VEGF and CXCR4 in tumor tissue of 5-Fu metronomic chemotherapy group, Fufang Kushen Injection group and combined treatment group were significantly lower than those of control group, protein levels of SDF-1 in tumor, liver and lung tissues were also significantly lower than those of control group, and those of combined treatment group were much lower than those of 5-Fu metronomic chemotherapy group and Fufang Kushen Iniection group, except for the protein level of SDF-1 in liver tissue. Conclusions： Fufang Kushen Injection combined with metronomic chemotherapy of 5-Fu can inhibit the expressions of VEGF, CXCR4 and SDF-1 synergistically in tumor tissues, which might be the mechanism of its anti-angiogenesis effect.