Distinct Mitochondrial Recovery Dynamics Following Taxol Removal in Triple-Negative Breast Cancer Cells

Drug resistance in TNBC is associated with metabolic plasticity, yet little is known about how mitochondrial and cellular states evolve after chemotherapeutic withdrawal. We used optical redox imaging (ORI) microscopy and complementary functional measurements to characterize post-Taxol recovery in two TNBC cell lines with different Taxol sensitivities. Whole-dish nuclear counting following 48 h Taxol treatment confirmed that HCC1806 cells responded at lower Taxol concentrations than MDA-MB-436 cells. Recovery was subsequently monitored following extracellular Taxol withdrawal using mitochondrial redox indices, mitochondrial reactive oxygen species (mito-ROS), mitochondrial membrane potential (MMP), multinucleation, and live- and dead-cell counts. HCC1806 cells showed substantial recovery of several mitochondrial parameters and resolution of multinucleation by 96 h; however, a late reductive shift in the optical redox ratio (ORR), reduced MMP, and attenuated live-cell population expansion indicated incomplete redox and functional recovery. In contrast, MDA-MB-436 cells exhibited persistent elevations in Fp and ORR through 144 h, residual multinucleation, and little sustained live-cell population expansion. These findings demonstrate that mitochondrial, multinucleation, and population-level recovery can proceed on different timescales and that post-treatment recovery differs markedly between TNBC models with different Taxol sensitivities. Longitudinal ORI provides a non-destructive approach for characterizing persistent post-treatment metabolic states and, together with functional measurements, may facilitate investigation of recovery-associated phenotypes relevant to therapeutic response.