Cytotoxic and biomechanical effects of clinical dosing schemes of paclitaxel on neurons and cancer cells.

Abstract

Chemotherapy-induced peripheral neuropathy often results in a reduction in drug dose. However, the serum level of anticancer drugs varies with time after intravenous infusion, and this factor has seldom been considered in previous in vitro studies. The goals of this study were to build an automatic dosage control system and to evaluate the influence of drug infusion rate on the cells. Neurons and melanoma cells were used as the samples. The 3-h (average and peak concentration: 0.024 and 0.287μM) and 24-h infusion (average and peak concentration: 0.020 and 0.042μM) schemes were investigated. For evaluations, cell indentation tests by an atomic force microscope, serial immunofluorescent images, and cell viability analysis was performed. For the neurons, Young's modulus first increased and then remained unchanged in the 3-h scheme, but was stationary throughout the observation period in the 24-h scheme. For the cancer cells, Young's modulus increased in both infusion schemes, and the increase was larger in the 3-h scheme. Morphologically, axons swelled and shortened, and the number of their branches decreased in the 3-h scheme. In contrast, there was only slowed growth of axons without obvious morphological changes in the 24-h scheme. Viability analysis of the cancer cells revealed that the 3-h scheme had a better anticancer effect. A dosage-control system simulating the pharmacodynamic changes of drugs was successfully constructed for in vitro cell cultures. The 3-h scheme of paclitaxel showed better anticancer effects but more adverse effects on neuronal growth and morphology.