Fig. 7

PI3K pathway inhibition with copanlisib leads to degradation of Cyclin D1 via the proteasome and sensitization to CDDP but not radiation. (A) Western blot representing downregulation of Cyclin D1 upon gene silencing or after treatment of 0.5 µM copanlisib for 24 h. This effect was reversed by treatment of the proteasome inhibitor MG132 (10 µM for 4 h). Samples were derived from the same experiment, and gels and blots were processed in parallel. Original blots are presented in Supplementary Image S2; (B) VEGF levels decreased upon copanlisib treatment (0.5 µM for 24 h); (C) Dose-response curves for copanlisib; (D-E) FaDu c5 and UM-22B, two HNSCC cell lines overexpressing Cyclin D1 were pretreated for 24 h with copanlisib before CDDP treatment (D) or irradiation with 4 Gy (E). Viability assay by MTT was done after 72 h (D) or 48 h (E). Bars represent ± SEM from at least three independent experiments.