Biological and Biomechanical Effects of Clinical Dosing Schedule of Paclitaxel on Neurons and Cancer Cells

  • 楊 芷璇

Student thesis: Doctoral Thesis

Abstract

Chemotherapy-induced peripheral neuropathy(CIPN) often results in dose reduction or therapy termination The goal of this study is to build an automatic system which can simulate the pharmacokinetics of 3-hr or 24-hr paclitaxel treatment (dose:135 mg/m2) by several unit step functions and use it to evaluate the influences of two infusion schedules on biological and biomechanical changes of neurons and cancer cells Dorsal root ganglion (DRG) neurons from C57BL/6 and melanoma cells (B16F10) were used as samples and three observation times were set for each infusion schedule The results of image analysis of neuron cells showed that axonal swellings were found with accumulation of microtubules and neurofilaments in both schedules Besides 3-hr infusion shortened the length of axons and was detrimental to axon branches However 24-hr infusion just slowed the growth rate Viability analysis revealed that 3-hr infusion has better anticancer effect The atomic force microscope (AFM) indentation tests were performed on somas of DRG neuron cells and B16F10 cells For DRG neuron cells the results showed that Young's modulus first increased and then remained unchanged in 3-hr infusion In contrast the Young's modulus declined slightly on the last observation time in 24-hr infusion For the B16F10 cells Young's modulus increased in both infusion schedules and the values of 3-hr infusion increased more than those in 24-hr infusion In summary although 3-hr infusion showed better anticancer effect it made microtubules of neurons be liable to accumulate at somas and shortened the axons Therefore 3-hr infusion may be more likely to induce CIPN
Date of Award2019
Original languageEnglish
SupervisorMing-Shaung Ju (Supervisor)

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