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: Xuechi Lin, Ying Liao, Xian Chen, Dan Long, Ting Yu, Fang Shen
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 31 Issue 2 Pg. 37-43 (Mar 2016) ISSN: 1557-8852 [Electronic] United States
• PMID: 26881937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• RNA, Messenger
• STMN1 protein, human
• Stathmin
• Extracellular Signal-Regulated MAP Kinases
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Autocrine Communication
• Blotting, Western
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Paclitaxel (pharmacology)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Stathmin (metabolism)
• Tumor Cells, Cultured