Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux.

摘要: Multidrug resistance (MDR) is a phenomenon by which cancer cells evade the cytotoxic effects of chemotherapeutic agents. It may occur through different mechanisms, but it often correlates with overexpression integral membrane transporters, such as P-glycoprotein (Pgp) and MDR-associated proteins (MRPs), resulting decrease drug accumulation cellular death. Doxorubicin substrate Pgp; has been suggested that its ability to induce synthesis nitric oxide (NO) could explain, at least in part, effects. Culturing human epithelial colon cell line HT29 presence doxorubicin, we obtained doxorubicin-resistant (HT29-dx) population: these accumulated less intracellular were sensitive doxorubicin cisplatin, overexpressed Pgp MRP3, exhibited lower NO production (both under basal conditions after stimulation). The be reversed when HT29-dx incubated inducers (cytokines mix, atorvastatin). Some donors increased guarosine-3':5'-cyclic monophosphate-independent way; this effect was associated marked reduction efflux rate cells, tyrosine nitration MRP3 protein. Our results suggest onset MDR impairment are related; finding point new strategy reverse cancer.