CXCL12及AMD3100对神经母细胞瘤细胞增殖及转移的影响

Effects of CXCL12 and the receptor antagonist AMD3100 on the proliferation and migration of neuroblastoma cells

目的探讨CXCL12（SDF-1，基质细胞衍生因子-1）对神经母细胞瘤（neuroblastoma，NB）细胞体外增殖及迁移的影响及CXCL12受体拮抗剂AMD3100对其阻断作用。方法用浓度为100ng／mlCXCL12刺激人神经母细胞瘤细胞系QDDQ-NM、SK—N-SH、SH—SY5Y三组细胞，MTT法检测CXCL12对神经母细胞瘤细胞增殖的促进作用。用不同浓度的CXCL12（0、30、50、100ng／m1）诱导三组细胞，Transwell体外趋化迁移实验检测三组神经母细胞瘤细胞迁移能力，再用100ng／mlAMD3100孵育三组细胞后应用CXCLl2诱导，Transwell体外趋化迁移实验检测三组神经母细胞瘤细胞迁移能力的变化。结果MTT结果示在一定时间范围内，CXCL12可促进QDDQ-NM、SH—SY5Y神经母细胞瘤细胞增殖，效果随着时间的延长而增强，在48h时，促进增殖效应达最大，与空白调零组及空白对照组比较有明显差异（P〈0．05）。Transwell体外趋化侵袭实验表明：CXCL12可促进QDDQ-NM、SHSY5Y神经母细胞瘤细胞的迁移能力，迁移细胞数明显高于对照组（P〈0．05），在一定范围内，CXCLl2为50g／ml时作用最强（P％0．01）；且AMD3100均可抑制三组细胞迁移能力（P〈O．05）。结论CXCR4-CXCLl2生物学轴在神经母细胞瘤细胞增殖及嗜器官特异性转移侵袭过程中发挥了重要作用，而AMD3100可阻断神经母细胞瘤的增殖、侵袭能力。

Objective To investigate the effects of CXCL12 and its receptor antagonist AMD3100 on the proliferation and migration of neuroblastoma cell lines. Methods MTT assay was used to test the effects of CXCLI2 on the proliferation of QDDQ-NM, SK-N-SH and SH-SY5Y neuro- hlastoma cell lines. The cell lines were induced by different concentrations of CXCL12 （0, 30, 50, 100 ng/ml）, and the metastatic potential detected by the transwell in-vitro invasion assay. Then 100ng/ml of AMD3100 was added to the transwen to evaluate its potential inhibition of the metastasis. Results The promotion effects of CXCL12 on the proliferation of the QDDQ-NM, SH-SY5Y neuroblastoma cells depended on time. The most profound effect on proliferation was seen at 48hr. Transwell in-vitro invasion assay indicated that the ability of QDDQ-NM and SK-N-SH neuroblastoma cells migration and invasion were enhanced significantly by CXCL12 （P〈0. 05）, with 50ng/ml CXCL12 being the best dosage （P%0. 01）. AMD3100 could inhibit cell migration and invasion （P%0. 05）. Conclusions CX- CL12 plays an important role on the neuroblastoma cells proliferation and migration, and AMD3100 can block the effect of CXL12.