title: Insulin-like growth factor-1 attenuates apoptosis and protects neurochemical phenotypes of dorsal root ganglion neurons with paclitaxel-induced neurotoxicity in vitro.
abstract: Paclitaxel (PT)-induced neurotoxicity is a significant problem associated with successful treatment of cancers. Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 has protective effects on neurite growth, cell viability, neuronal apoptosis and neuronal phenotypes in DRG neurons with PT-induced neurotoxicity is still unclear. In this study, primary cultured rat DRG neurons were used to assess the effects of IGF-1 on DRG neurons with PT-induced neurotoxicity. The results showed that PT exposure caused neurite retraction in a dose-dependent manner. PT exposure caused a decrease of cell viability and an increase in the ratio of apoptotic cells which could be reversed by IGF-1. The percentage of calcitonin gene-related peptide immunoreactive (CGRP-IR) neurons and neurofilament (NF)-200-IR neurons, mRNA, and protein levels of CGRP and NF-200 decreased significantly after treatment with PT. IGF-1 administration had protective effects on CGRP-IR neurons, but not on NF-200-IR neurons. Either extracellular signal-regulated protein kinase (ERK1/2) inhibitor PD98059 or phosphatidylinositol 3-kinase (PI3 K) inhibitor LY294002 blocked the effect of IGF-1. The results imply that IGF-1 may attenuate apoptosis to improve neuronal cell viability and promote neurite growth of DRG neurons with PT-induced neurotoxicity. Moreover, these results support an important neuroprotective role of exogenous IGF-1 on distinct subpopulations of DRG neurons which is responsible for skin sensation. The effects of IGF-1 might be through ERK1/2 or PI3 K/Akt signaling pathways. These findings provide experimental evidence for IGF-1 administration to alleviate neurotoxicity of distinct subpopulations of DRG neurons induced by PT.
authors.affiliation: a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: b Department of Cardiosurgery , Shandong University Qilu Hospital , Jinan , Shandong Province , China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Bi
authors.affiliation: c Department of Histology and Embryology , Binzhou Medical College , Binzhou , China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Liu
authors.affiliation: d Department of Orthopaedics , Shandong University Qilu Hospital , Jinan , Shandong Province , China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: a Department of Anatomy , Shandong University School of Medicine , Jinan , Shandong Province , China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: e Department of Rheumatology , Shandong University Qilu Hospital , Jinan , Shandong Province , China.
authors.forename: Huaxiang
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000066829:Neuroprotection; D017239:Paclitaxel / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000009:adverse effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D050257:Tubulin Modulators; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D017239:Paclitaxel
keywords: Apoptosis; Calcitonin gene-related peptide; Dorsal root ganglion; Insulin-like growth factor-1; Neurofilament-200; Paclitaxel