title: Activation of AKT/ERK confers non-small cell lung cancer cells resistance to vinorelbine.
abstract: Vinorelbine is a semi-synthetic vinca-alkaloid approved for the treatment of non-small cell lung cancer (NSCLC). However, the lower objective response rate and higher adverse effects of vinorelbine hinder its wide use in treatment of advanced NSCLC. Therefore, it is of great interest to uncover the biomarkers for sensitivity of NSCLC cells to vinorelbine to allow the identification of patients most likely to benefit from vinorelbine-based chemotherapy and to improve the therapy. In present work, four NSCLC cell lines were divided into vinorelbine-sensitive (VS) group and vinorelbine-resistant (VR) group according to their sensitivities to vinorelbine. And then the gene expression profiles of these two groups was compared, the differentially expressed genes (expression difference higher than 100% and p<0.05, totally 496 genes) were applied to Ingenuity Pathway Analysis (IPA). IPA results showed that NF-κB and PTEN signaling were predicted to be inactivated in VR cell lines, which was partially validated by quantitative PCR or western blotting experiments. The higher expression of RAF1 mRNA and the activation of AKT/ERK proteins in VR NSCLC cell lines may confer resistance to vinorelbine. Our work may provide potential pathway signature for vinorelbine sensitivity and some therapeutic targets for combined therapy.
authors.affiliation: Department of Respiratory Medicine, First Clinical Medical College Affiliated to Harbin Medical University Harbin, China.
authors.forename: Da-Ping
authors.initials: DP
authors.lastname: Fan
authors.affiliation: Department of Respiratory Medicine, First Clinical Medical College Affiliated to Harbin Medical University Harbin, China.
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, First Clinical Medical College Affiliated to Harbin Medical University Harbin, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Hu
authors.affiliation: Department of Respiratory Medicine, First Clinical Medical College Affiliated to Harbin Medical University Harbin, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, First Clinical Medical College Affiliated to Harbin Medical University Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D059467:Transcriptome; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D000077235:Vinorelbine
keywords: AKT; ERK; NF-κB signaling; Non-small cell lung cancer; PTEN signaling; vinorelbine