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目的:探讨低氧微环境对人乳腺癌细胞株MDA-435中基质金属蛋白酶(matrix metalloproteinases,MMPs)及其抑制剂(tissue inhibitors of matrix metalloproteinases,TIMPs)表达的影响。方法:分别置人乳腺癌细胞株MDA-435于常氧(21%O25、%CO2)和低氧(1%O25、%CO2和94%N2)环境中培养6 h,RT-PCR技术mRNA水平检测MMP2、9及TIMP2、1的表达。结果:MDA-435细胞株表达MMP9和TIMP1 mRNA,未检测到MMP2和TIMP2mRNA;低氧环境下MDA-435细胞株中MMP9 mRNA水平显著上升(P<0.05),TIMP1基因的表达在低氧环境与常氧环境下差异无统计学意义(P>0.05)。结论:与常氧环境相比,低氧环境下乳腺癌细胞株MDA-435中MMP9及其抑制剂TIMP1的表达平衡发生了改变,提示,进行肿瘤转移分子机制的体外研究应充分考虑氧环境的影响。
Objective: To investigate the effect of hypoxia microenvironment on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in human breast cancer cell line MDA-435. Methods: Human breast cancer cell line MDA-435 was cultured for 6 h under normoxia (21% O25% CO2) and hypoxia (1% O25% CO2 and 94% N2) The expression of MMP2,9 and TIMP2,1 were detected. Results: The expression of MMP9 and TIMP1 mRNA in MDA-435 cell line did not detect MMP2 and TIMP2 mRNA. The expression of MMP9 mRNA in MDA-435 cell line increased significantly under hypoxia (P <0.05). The expression of TIMP1 gene in hypoxia No significant difference under normoxic conditions (P> 0.05). CONCLUSION: Compared with normoxic environment, the expression of MMP9 and its inhibitor TIMP1 in breast cancer cell line MDA-435 under hypoxia environment changes, suggesting that the molecular mechanism of tumor metastasis in vitro should take full account of the oxygen environment influences.