Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-?b signalling in LPS-induced PC3 cells
Küçük Resim Yok
Tarih
2016
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Via Medica
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Introduction. Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-?B) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-?B signaling. Material and methods. PC3 cells were incubated with LPS (0.5 µg/mL) for 24 h in the presence or absence of doxycycline (5 µg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-?B/p65, I?B-?, p-I?B-?, IKK-ß were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography. Results. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-?B/p65, p-I?B-?, IKK-ß and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and I?B-a was affected by neither LPS nor doxycycline. Conclusions. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-?B signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells. ©Polish Society for Histochemistry and Cytochemistry.
Açıklama
Anahtar Kelimeler
Doxycycline, Immunohistochemistry, MMPs, NF-?B, PC3 cells, Prostate cancer, Western blotting, Zymography
Kaynak
Folia Histochemica et Cytobiologica
WoS Q Değeri
Scopus Q Değeri
Q3
Cilt
54
Sayı
4