| Summary: | 碩士 === 國立成功大學 === 機械工程學系 === 105 === Chemotherapy-induced peripheral neuropathy (CIPN) is by far the top reason for patients to drop out of chemotherapy. 50% of patients suffer from CIPN after treated with paclitaxel, a cytotoxicity drug which targets microtubules of cells and kills it by disrupting the cell cycle. Most of CIPN symptoms is related to dysfunction or damage of patients’ neurons. This study focus on effect of paclitaxel concentrations effect on neuron cells. PC-12 cells are used as the model of neuron cells in this study. The morphological effect is examined using immunofluorescence staining. Multi indexes, include an index describing the dispersion of microtubules near nucleus area called dispersion ratio (RD), are then examined by processing cell images using software ImageJ. The biomechanical effect is tested using an atomic force microscope (AFM). Cell topography was first scanned and then indentation experiments of different area (nucleus and transition area) were performed. Cell high was measured by topographies and local apparent Young’s modulus was estimated by fitting the force-indentation data to the bottom-effect-cone-correction (BECC) model. This study find that paclitaxel affects the dispersion of microtubules in cells. The dispersion ratio increase with the increase of concentration of paclitaxel. This result suggests that there are more microtubules assembled in nucleus area of cells affected by paclitaxel, rather than spread through the whole soma or axon. The Young’s modulus of both nucleus and transition area of paclitaxel effected cells are higher than control group except the transition area of 1 μM group. Also, as the concentration of paclitaxel increase, the Young’s modulus increase. Combine these two results, this study suggests that paclitaxel enhance assembly of microtubules in area near nucleus, leading to the Young’s modulus increase. And the disorder or incorrect distribute of microtubules can cause dysfunction of neurons, which may result in CIPN.
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