Figure 5 from Oncogenic Mutant <i>p53</i> Sensitizes Non–Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress–Dependent Induction of Mitochondrial Apoptosis

<p>Navitoclax enhances BTZ-induced cytotoxicity. <b>A</b> and <b>B,</b> H1975 and H460 cells were treated with vehicle or the indicated concentrations of navitoclax with/without BTZ (2 nmol/L) for 96 hours. Cell viability was determined by WST-1 assay. <b>C,</b> H1975-Control or H1975-p53KO cells were treated with vehicle or the indicated concentrations of navitoclax with/without BTZ (5 nmol/L) for 96 hours. Cell viability was determined by WST-1 assay. <b>D</b> and <b>E,</b> NOD-SCID-II.2 receptor gamma null (NSG) mice were injected with 3.0 × 10⁶ H1975 (<b>D</b>) or 1.0 × 10⁶ H460 cells (<b>E</b>), and once tumors became palpable, mice were treated for 3 weeks with vehicle (control) or the combination of BTZ (1.0 mg/kg) 2×/week via intraperitoneal injection + navitoclax (NAV; 80 mg/kg) 3×/week via oral gavage + carboplatin (CBP; 25 mg/kg) once weekly via intraperitoneal injection. The period of treatment is indicated by the horizontal bar, and tumor volumes were measured twice weekly (<i>N</i> = 6 mice/group). *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.005; ns indicates <i>P</i> > 0.05. Error bars indicate ± 1.0 SD., except in <b>D</b> and <b>E</b> in which error bars indicate SEM.</p>

Duke Scholars

Author Eziafa I Oduah Medicine, Medical Oncology