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Objective To explore the effects of low density lipoprotein(LDL) containing immune complexes(IC) on the mRNA expression of matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-1(TIMP-1) in U937 cells.Methods U937 cells were incubated with native LDL,oxidized LDL or LDL-IC,respectively.mRNA expression of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in U937 cells were measured by reverse transcriptase polymerase chain reaction(PT-PCR).Results Normal U937 cells hardly expressed MMP-1,but highly expressed TIMP-1.N-LDL had no effect on the expression of MMP-1 and TIMP-1 mRNA.Ox-LDL can induce slightly expression of MMP-1 and markedly down-regulate expression of TIMP-1.Similarly,nature and oxidized LDL-IC had significantly more effect on the mRNA expressions of MMP-1 and TIMP-1 than that of control(P
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Matrix metalloproteinases(MMP) are a family of Zn~(2+)-dependent endopeptidases capable of cleaving components of extracellular matrix(ECM).MMP-1 was the first vertebrate collagenase purified as a protein and cloned as a cDNA,and is considered the prototype for all the interstitial collagenases.It is synthesized as a zymogen.Its N-terminal residues are removed by proteolysis and it shares with other MMPs a catalytic domain and a carboxy terminal domain with the sequence similar to hemopexin.(MMP-1) should be considered as a multifunctional molecule since it participates not only in the turnover of collagen fibrils in the extracellular space but also in the cleavage of a number of nonmatrix substrates and cell surface molecules,suggesting an important role in the regulation of cellular behaviour.Furthermore,an extensive body of evidence indicates that MMP-1 plays an important role in diverse physiologic processes such as growth,tissue morphogenesis,and wound repair.Likewise,it seems to be implicated in a variety of human diseases including atherosclerosis,rheumatoid arthritis,pulmonary emphysema,and fibrotic disorders,suggesting that its inhibition or stimulation may open therapeutic avenues.
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Objective To investigate whether nobiletin could enhance chemotherapeutic drug-induced cell proliferation inhibition and apoptosis in breast carcinoma cells MDA-MB-231 in vitro.Methods MDA-MB-231 cells were exposed to nobiletin and different chemotherapeutic drugs at different concentration.The cell proliferation inhibitory rate was observed by MTT,apoptosis was detected by DNA Ladder,flow cytometry (FCM),and ELISA,and an NF-?B electrophoretic mobility shift was conducted by EMSA and ELISA.Results The combination of nobiletin (20 ?mol) with Taxol (1 nmol) or Doxorubicin (50 ng/mL) resulted in a significant inhibitory rate of cell growth and more apoptosis in MDA-MB-231 cells of 75.1% and 82.6% compared with either of them alone (40% and 45%),respectively.DNA Ladder and FCM assay showed that nobiletin could promote the cell apoptosis induced by chemotherapeutic drug.EMSA and ELISA assay showed that nobiletin could inhibit NF-?B activity in nuclear and cytoplasm of MDA-MB-231 cells.Conclusion The current results suggest that nobiletin could enhance the inhibition of chemotherapeutic drug on cell proliferation and cell apoptosis of breast carcinoma cells MDA-MB-231,the mechanism may be related to down-regulate the NF-?B activity in vitro.