Celecoxib inhibits MDR1 expression through COX-2-dependent mechanism in human hepatocellular carcinoma (HepG2) cell line

dc.contributor.author Roy, Karnati R.
dc.contributor.author Reddy, Gorla V.
dc.contributor.author Maitreyi, Leela
dc.contributor.author Agarwal, Smita
dc.contributor.author Achari, Chandrani
dc.contributor.author Vali, Shireen
dc.contributor.author Reddanna, Pallu
dc.date.accessioned 2022-03-27T01:04:14Z
dc.date.available 2022-03-27T01:04:14Z
dc.date.issued 2010-04-01
dc.description.abstract The role of COX-2 in the regulation of the expression of MDR1, a P-glycoprotein involved in hepatocellular carcinoma cell line, HepG2, was studied in the present investigation. Celecoxib, a selective inhibitor of COX-2, at 25 μM concentration increased the accumulation of doxorubicin in HepG2 cells and enhanced the sensitivity of the cells to doxorubicin by tenfold. The induction of MDR1 expression by PGE2 and its downregulation by celecoxib or by COX-2 knockdown suggests that the enhanced sensitivity of HepG2 cells to doxorubicin by celecoxib is mediated by the downregulation of MDR1 expression, through COX-2-dependent mechanism. Further studies revealed the involvement of AP-1 in the celecoxib-induced downregulation of MDR1 expression. These experimental studies correlated well with in silico predictions and further suggested the inactivation of the signal transduction pathways involving ERK, JNK and p38. The present study thus demonstrates the usefulness of COX-2 intervention in overcoming the drug resistance in HepG2 cells. © 2009 Springer-Verlag.
dc.identifier.citation Cancer Chemotherapy and Pharmacology. v.65(5)
dc.identifier.issn 03445704
dc.identifier.uri 10.1007/s00280-009-1097-3
dc.identifier.uri http://link.springer.com/10.1007/s00280-009-1097-3
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/4065
dc.subject AP-1
dc.subject Celecoxib
dc.subject COX-2
dc.subject HepG2 cells
dc.subject MDR1
dc.subject Simulation
dc.title Celecoxib inhibits MDR1 expression through COX-2-dependent mechanism in human hepatocellular carcinoma (HepG2) cell line
dc.type Journal. Article
dspace.entity.type
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