The influence of opioids on matrix metalloproteinase-2 and -9 secretion and mRNA levels in MCF-7 breast cancer cell line
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Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in degradation of extracellular matrix, a process that initiates uncontrolled spread of proliferating cancer cells and therefore plays a crucial role in cancer invasion and metastasis. Compounds able to modulate MMP activity may become important tools in cancer research. In the present study we examined the effect of two μ-selective opioids, morphine and endomorphin-2 (EM-2) on the production of MMP-2 and MMP-9 in MCF-7 cells. We report that both opioids time- and concentration-dependently inhibited the expression and secretion of these MMPs. The observed effect was not reversed by naloxone (Nal). Further experiments showed that morphine and EM-2 decreased endothelial nitric oxide synthase (eNOS) mRNA level and nitric oxide (NO) secretion in MCF-7 cells. These findings indicate that attenuation of MMP secretion by opioids was not mediated by opioid receptors but was under the control of nitric oxide system.
KeywordsNitric oxide synthase Biochemical markers ELISA assay RT-PCR
This work was supported by the grants from Polish Ministry of Science (No NN 401 0155 36) and the Medical University of Lodz (No 503-1156-2). The authors wish to thank Jozef Cieslak for his excellent technical assistance.
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