• Biao Xu, Jingyuan Li, Dehong Xu, and Qijie Ran.
• Department of Hematology, General Hospital of Central Theater Command, Wuluo Road 627th, Wuhan, 420015, China.
• Ir J Med Sci. 2023 Apr 1; 192 (2): 561567561-567.

ObjectiveThe anti-tumor effect of polo-like kinase 4 (PLK4) inhibitor has been explored in several neoplasms, while its synergy with bortezomib in multiple myeloma (MM) remains elusive. Hence, the present study aimed to investigate the effect of PLK4 inhibitor on the sensitivity of MM to bortezomib treatment and its underlying mechanism.MethodsMM cell lines (RPMI-8226 and U266) were cultured in different concentrations of CFI-400945 (PLK4 inhibitor), bortezomib, or their combination. Subsequently, 740 Y-P (PI3K activator) was added in the combination of CFI-400945 and bortezomib. Besides, cell viability and apoptosis were measured by CCK-8 reagent and TUNEL apoptosis kit, separately; meanwhile, western blot was carried out for detecting PLK4, p-PI3K, PI3K, p-AKT, and AKT.ResultsCFI-400945 and bortezomib decreased the cell viability in dose-dependent manners in MM cell lines, respectively. The combination of different concentrations of CFI-400945 and bortezomib reduced cell viability compared with monotherapy in MM cell lines (all P < 0.05). Interestingly, 200 nM CFI-400945 and 4 nM bortezomib showed the maximum synergy in MM cell lines. Furthermore, 200 nM CFI-400945 plus 4 nM bortezomib showed a better effect on decreasing cell viability and promoting cell apoptosis than CFI-400945 or bortezomib monotherapy in MM cells cell lines (all P < 0.05). Moreover, 740 Y-P alleviated the effect of bortezomib and CFI-400945 on PI3K/AKT signaling, cell viability, and apoptosis in MM cell lines.ConclusionsPLK4 inhibitor plus bortezomib shows synergy in decreasing cell viability and enhancing cell apoptosis via repressing PI3K/AKT signaling in MM.© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.

23 keywords...

hide…