RESUMEN
Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.
Asunto(s)
Animales , Ratas , Antirreumáticos , Química , Farmacología , Usos Terapéuticos , Artritis Experimental , Quimioterapia , Patología , Movimiento Celular , Núcleo Celular , Metabolismo , Células Cultivadas , Regulación Enzimológica de la Expresión Génica , Interleucina-1beta , Farmacología , Metaloproteinasa 13 de la Matriz , Genética , FN-kappa B , Genética , Metabolismo , Fosforilación , Transporte de Proteínas , Transducción de Señal , Sinoviocitos , Metabolismo , Activación Transcripcional , Triterpenos , Química , Farmacología , Usos TerapéuticosRESUMEN
Objective To investigate the effect of TRIM11(tripartite motif-containing protein 11) target regulating miR-24-3p on the proliferation and invasion of breast cancer cells,and potentiol relation between TRIM11 high ex-pression and the prognosis of breast cancer. Methods Immunohistochemical method was used to detect the expres-sion of TRIM11 in 31 cases of breast cancer and 31 cases of adjacent breast cancer normal tissues. The siRNA TRIM11 lentivirus and miR-24-3p lentivirus were transfected into human breast cancer MCF7 cell lines,observing the correlation expression of TRIM11 and miR- 24- 3p mRNA and protein by using real-time fluorescence quantitative PCR (RT-qPCR) and Western bolt,luciferase reporter experiments were used to verify that the miR-24-3p as a direct target of TRIM11,MTT and Transwell were used to investigate the cells proliferation,activity and invasion. Results The expression of TRIM11 in breast cancer tissues or MCF7 cells was significantly higher (P<0.05),and TRIM11 high expression predicts poor prognosis of breast cancer(P<0.05). siRNA TRIM11 significantly inhibited the expression of TRIM11 in MCF7 cells,moreover,which inhibited the MCF7 cells proliferation,viability and invasion (P<0.05). miR-24-3p significantly reduced 3′-UTR TRIM11 luciferase activity in wild-type (P<0.05),but no effect was found in mutant type.The expression of miR-24-3p was decreased,miR-24-3p and TRIM11 mRNA expression was negatively correlated in MCF7 cells(P<0.05),miR-24-3p inhibition protein and mRNA ex-pression of TRIM11 in MCF7 cells,and inhibit MCF7 cells proliferation,viability and invasion (P<0.05). Conclu-sions The expression of TRIM11 is up-regulated in breast cancer and cells,promote the proliferation and invasion of breast cancer cells though regulating miR-24-3p expression,TRIM11 high expression predicts poor prognosis of breast cancer,TRIM11/miR-24-3p axis is expected to become a new target for treatment of breast cancer.
RESUMEN
Fibroblast-like synoviocytes (FLS) play a pivotal role in Rheumatoid arthritis (RA) pathogenesis through aggressive migration and invasion. Madecassoside (Madec), a triterpenoid saponin present in Centella asiatica herbs, has a potent anti-inflammatory effect. In the present study, Madec exerted an obvious therapeutic effect in reversing the histological lesions in adjuvant-induced arthritis (AIA) rats. To recognize the anti-rheumatoid potentials of Madec, we further investigated whether Madec interfered with FLS invasion and metalloproteinase (MMP) expression. In cultures of primary FLS isolated from the AIA rats, Madec (10 and 30 μmol·L) was proven to considerably inhibit migration and invasion of FLS induced by interleukin 1β (IL-1β), but exhibiting no obvious effect on cell proliferation. Madec repressed IL-1β-triggered FLS invasion by prohibiting the expression of MMP-13. Additionally, Madec suppressed MMP-13 transcription via inhibiting the MMP-13 promoter-binding activity of NF-κB. Our results further showed that Madec down-regulated the translocation and phosphorylation of NF-κB as demonstrated by Western blotting and immunofluorescence assays. In conclusion, our results suggest that Madec exerts anti-RA activity via inhibiting the NF-κB/MMP-13 pathway.