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.

Keywords:

• Paclitaxel
• Apoptosis
• Insulin-like growth factor-1
• Calcitonin gene-related peptide
• Neurofilament-200
• Dorsal root ganglion

Acknowledgements

This work is supported by the National Natural Science Foundation of China (no. 81000517), the Shandong Provincial Natural Science Foundation of China (no. ZR2011HQ011), the Science and Technology Development Project of Jinan Municipality of Shandong Province of China (no. 201302040), and the Innovation Foundation of Shandong University (no. 2012TS125).

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Contributors

H.L. conceived and designed the experiments. C.C. and X.B. performed the experiments. Y.B. and H.L. analyzed the data. G.L. contributed reagents/materials/analysis tools. Z.L.wrote the paper.

Funding

None.

Conflicts of interest

None.

Ethics approval

All procedures described herein were reviewed by and had prior approval by the Ethical Committee for Animal Experimentation of the Shandong University. All surgeries were performed under anesthesia, and all efforts were made to minimize suffering of the animals.