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SDF-1/CXCR4对结直肠癌肝转移瘤表达乙酰肝素酶的影响

Effects of SDF-1 and CXCR4 on HPA Expression in Liver Metastases Induced by Colorectal Cancer Cells

  • 摘要: 目的 研究基质细胞衍生因子1(stromal cell derived factor-1,SDF-1)对高表达趋化因子受体CXCR4的结直肠癌Lovo细胞表达乙酰肝素酶(heparanase, HPA)的影响,并探讨 SDF-1/CXCR4轴对裸鼠结直肠癌肝转移瘤模型中乙酰肝素酶表达的影响。 方法 分别用SDF-1和SDF-1/CXCR4的拮抗剂AMD3100处理直肠癌 Lovo细胞,运用RT-PCR和免疫细胞化学技术检测结直肠癌细胞HPA 的表达;建立裸鼠结直肠癌肝转移瘤模型,检测AMD3100干预和非干预组转移瘤细胞中HPA 蛋白的表达。 结果 (1)结直肠癌Lovo细胞经不同浓度(50 ng/ml、100 ng/ml、200 ng/ml )SDF-1处理后,HPA mRNA的表达量逐渐增高。用相同浓度SDF-1分别处理直肠癌Lovo细胞12h和24h后,其HPA的表达量随作用时间的延长而增高。在相同作用时间内,其HPA的表达量随SDF-1作用浓度(50 ng/ml、100 ng/ml 、200 ng/ml)的升高而增高。(2)SDF-1处理组HPA 的mRNA和蛋白表达水平均高于SDF-1+AMD3100处理组和对照组。(3)肝脏转移瘤中HPA的表达量随AMD3100治疗剂量的增高而降低。 结论 (1)SDF-1可刺激结直肠癌Lovo细胞HPA表达增加,并且这一效应与SDF-1的浓度和作用时间有关。(2)AMD3100能有效抑制SDF-1刺激结直肠癌细胞表达HPA,使得肿瘤细胞侵袭能力下降,从而起到抑制肿瘤转移的作用。

     

    Abstract: Objective To study the effects of stromal cell derived factor 1 (SDF-1) on the expression of heparanase (HPA) of colorectal Lovo cells highly expressing chemotactic factor receptor CXCR4,and to explore the effects of SDF-1/CXCR4 on the expression of HPA in colorectal liver metastasic model in nude mice. Methods Colorectal Lovo cells were treated respectively with SDF-1 and AMD3100, an antagonist of SDF-1/CXCR4. The expression of HPA was detected by RT-PCR and immunocytochemical. Colorectal liver metastases model in nude mice was established. The expression of HPA protein of metastatic tumor cells treated or untreated with AMD3100 was detected respectively in liver metastases model. Results (1) The expressions of HPA mRNA increased gradually in colorectal Lovo cells treated with different concentrations of SDF-1(50 ng/ml, 100 ng/ml, 200 ng/ml). When treated with the same concentration of SDF-1 at different duration time, 12 and 24 hours,HPA expression increased gradually with the prolonged treating time. When the cells were treated with different concentrations of SDF-1(50 ng/ml, 100 ng/ml, 200 ng/ml) at the same duration time, HPA expression increased gradually with the increasing SDF-1 concentrations. (2) The mRNA and protein expression of HPA in SDF-1 treated group was higher than that in control group or the group treated with SDF-1 and AMD3100. (3) The expression of HPA of liver metastatic tumor cells decreased with the increasing of AMD3100. Conclusion (1) The expression of HPA of colorectal Lovo cells is able to be induced by SDF-1 in a concentration- or time-dependent manner. (2) AMD3100 could inhibit HPA expression stimulated by SDF-1 and may inhibit tumor metastasis.

     

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