title: Regulation of Oncoprotein 18/Stathmin Signaling by ERK Concerns the Resistance to Taxol in Nonsmall Cell Lung Cancer Cells.
abstract: 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.
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .|2 Department of Clinical Laboratory, Hunan Normal University , Changsha, Hunan.
authors.forename: Xuechi
authors.initials: X
authors.lastname: Lin
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .|3 Department of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University , Changsha, China .
authors.forename: Ying
authors.initials: Y
authors.lastname: Liao
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .
authors.forename: Xian
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .
authors.forename: Ting
authors.initials: T
authors.lastname: Yu
authors.affiliation: 1 Department of Medical Laboratory, Changsha Medical University , Changsha, China .|2 Department of Clinical Laboratory, Hunan Normal University , Changsha, Hunan.
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050777:Stathmin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D048049:Extracellular Signal-Regulated MAP Kinases; D017239:Paclitaxel
keywords: ERK; Op18/stathmin; nonsmall cell lung cancer; signal regulation; taxol resistance