Figure 4

Pharmacological clearance of senescent cells with ABT263 reverses CIPN in mice. (a) Treatment regimen to induce CIPN and then remove senescent cells with ABT263 in C57BL/6 mice. (b) Response of WT mice to mechanical stimulation, as measured by von Frey tests, before and after treatment with 2.3 mg/kg cisplatin (n = 5, P = 0.0067, 0.0103, 0.0153, and 0.0027 on days 15, 25, 65, and 87 for cisplatin-vehicle group and P = 0.0001 and 0.0002 on days 15 and 25 for cisplatin-ABT263 group). Senescent cells were removed in half the cisplatin-treated mice with 50 mg/kg ABT263 (n = 5, P = 0.0271 and 0.0053). Response of the same mice to (c) thermal stimulation, as measured by hot plate tests, was measured after cisplatin ± ABT263 treatment (P = 0.0027 and 0.1266). The control group (n = 10) received saline and was compared to the cisplatin group without ABT263 treatment (P = 0.0004 and 0.0306). (d, e) Senescent cell removal by ABT263 in the DRG of C57BL/6 mice 72 days after cisplatin treatment as shown by (d) p16Ink4a (P = 0.0191 and 0.0171) and (e) p21 expression (P < 0.0001 and < 0.0001). n = 7 or 3. Data points are mean values ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ^****P < 0.0001 denote significance levels detected by (b, C) two-way and (d, e) one-way ANOVA with post-hoc Tukey test.