The MDR phenotype is associated with the expression of COX-2 and iNOS in a human hepatocellular carcinoma cell line

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Ornella FantappièRoberto Mazzanti

Abstract

The presence of multiple drug resistance (MDR1) and angiogenic phenotypes negatively affect patients' prognosis with cancer even when treated with drugs that are not transported by the MDR1 gene product. It is possible to suggest a link between the MDR1 and angiogenic phenotypes. Because prostaglandins (PGs) and nitric oxide (NO) have been proposed to be involved in angiogenesis in vivo, the production of PGs and NO and the behavior of inducible NO synthase (iNOS), cyclooxygenase 1 (COX-1), and inducible cyclooxygenase (COX-2) were studied in parental drug-sensitive (P5) liver cancer cell lines and in P5-derived MDR1 cells P1(0.5). Immunohistochemical evaluation, Northern and Western blot analysis of COX-2 and iNOS, and assessment of cell proliferation were performed in basal conditions and after the exposure to stimulants or to specific inhibitors of COX-2 and iNOS. The messenger RNA and protein levels of COX-2 and iNOS were in basal conditions higher in P1(0.5) cells than the parental P5 cells. The exposure to lipopolysaccharide (LPS) or epidermal growth factor (EGF) determined an increase of PG and NO production in both cell lines and this increase was strongly reduced by COX-2 inhibitors such as celecoxib (CLX) and nimesuli...Continue Reading

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