低相对分子质量肝素联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响

摘要/Abstract

摘要： 目的探讨低相对分子质量肝素（LMWH）联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响及其相关的分子机制。方法
采用MTT法检测药物对鼻咽癌细胞CNE1、CNE2的增殖抑制效应；细胞划痕实验、Transwell小室法检测细胞的迁移和侵袭能
力；Western blot检测基质金属蛋白酶-9 （MMP-9）和基质金属蛋白酶组织抑制剂-1 （TIMP-1）的表达；ELISA法检测细胞培养液
中乙酰肝素酶（HPA）的表达。结果MTT结果显示，不同浓度LMWH和紫杉醇对鼻咽癌细胞CNE1、CNE2均具有显著的增殖
抑制作用。200 U·ml^-1LMWH与0.1μmol·L^-1紫杉醇联合作用于CNE1、CNE2细胞24 h的迁移抑制率分别为66.70%、70.53%，
较单用紫杉醇的迁移抑制率明显提高。同时LMWH与紫杉醇联合作用于CNE1、CNE2细胞的侵袭抑制作用也明显高于单用
紫杉醇的作用。LMWH与紫杉醇均可下调MMP-9和HPA的表达，且合用时作用更加明显。结论LMWH具有增强紫杉醇抑
制鼻咽癌细胞侵袭和迁移的作用，其机制可能与下调MMP-9和HPA的表达有关。

Abstract: ObjectiveTo investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the
invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms. MethodsMTT assay
was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and
Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay
was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor
of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of
heparanase (HPA) in the culture medium of the cells.ResultsMTT assay showed an obvious suppression of CNE1 and CNE2
cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1μmol·L PTX
for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectiuely significantly
higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a
significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of
MMP-9 and HPA induced by PTX.ConclusionLMWH can enhance the inhibitory effect of PTX on the migration and invasion
of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions

张配，赵素容，宋乐乐，浦龙健，蒋志文，刘浩，蒋琛琛. 低相对分子质量肝素联合紫杉醇对鼻咽癌细胞侵袭和迁移能力的影响[J]. 南方医科大学学报, 2012, 32(11): 1529-.

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