Taxol is a cytotoxic antiepithelioma chemotherapy drug widely used clinically, which results in appearing a broad range of taxol-resistant tumors. Oncoprotein 18 (Op18)/stathmin is a genetically highly conserved small-molecule cytosolic phosphoprotein and highly expressed in tumors. Extracellular signal-regulated kinase (ERK) is a main member of mitogen-activated protein kinases (MAPKs). The study demonstrated that combination of blockage of ERK signal by ERK inhibitor PD98059 and Taxol greatly promoted taxol-induced cellular apoptosis and growth inhibition, decreased the expression of Op18/stathmin and total levels of phosphor-Op18/stathmin, while weakened the cyclin-dependent kinase 2 (cdc2) activity and antiapoptotic protein Bcl-2 expression and inhibited IL-10 autocrine in taxol-resistant NCI-H1299 cells; Taxol-resistant NCI-H1299 cells expressed high levels of ERK and phosphor-ERK in contrast to taxol-sensitive CNE1 cells, and ERK mainly phosphorylated Op18/stathmin at Ser 25 site. These findings suggest that ERK-mediated Op18/stathmin is involved in taxol resistance of tumors; blockage of ERK signal improves the sensitivity of tumor cells to taxol, which provides new clues for treating taxol-resistant carcinomas.
Keywords: ERK; Op18/stathmin; nonsmall cell lung cancer; signal regulation; taxol resistance.