Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) remains a major reason for cancer patients to withdraw from their lifesaving therapy. CIPN results in irreversible sensory and motor impairments; however, the epidemiology is largely unknown. Here, we report for the first time that chemotherapy drug vincristine not only reduced axonal regeneration in primary dorsal root ganglion neuron but also induced substantial changes in cell mechanical properties detected by atomic force microscopy (AFM). Confocal imaging analysis revealed vincristine-induced microtubule depolymerization. By using AFM for high-resolution live cell imaging and quantitative analysis, we observed significant changes in cell surface roughness and stiffness of vincristine-treated neurons. Elastic modulus was decreased (21-45%) with increasing dosage of vincristine. Further study with paclitaxel, another well-known CIPN drug, confirmed the link between cell mechanics and cytoskeleton organization. These data support that our system can be used for probing potential CIPN drugs that are of enormous benefit to new chemotherapy drug development.
This study concludes that reduced cell elasticity in dorsal root ganglion neurons accompanies the development of chemotherapy-induced peripheral neuropathy, providing a model system that enables testing of upcoming chemotherapy agents for this particularly inconvenient and often treatment-limiting complication.
Patients withdraw from their life-saving treatment for cancer due to the development of chemotherapy-induced peripheral neuropathy (CIPN). There is an urge to establish a screening tool to identify chemotherapy drugs that could cause peripheral neuropathy. Here, we tested the effects of some well-known CIPN drugs on mouse primary peripheral sensory neurons by using atomic force microscopy (AFM). CIPN drugs significantly change the cell morphology and mechanical properties of sensory neurons, which was detected by AFM. We proposed that our in vitro system can serve as a cell-based screening tool for future chemotherapy drug discovery. [Display omitted]