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. Author manuscript; available in PMC: 2015 Mar 1.
Published in final edited form as: Cancer Discov. 2014 Jul 31;4(9):1022–1035. doi: 10.1158/2159-8290.CD-14-0098

Figure 5. pG1 sensitizes resistant BTKWT MCL cells to ibrutinib via synergic induction of PIK3IP1.

Figure 5

A, schema for dual targeting of BTK with ibrutinib and CDK4 with PD 0332991 in MCL cells expressing BTKWT. pG1: prolonged early G1 arrest that exceeds the schedule early G1 transit time (16–20 hours in MCL cells) by selective and sustained inhibition of CDK4. B, schema for sequential incubation with PD 0332991 (0.3 μmol/L) and ibrutinib (left), Total viable cells (x 20,000 cells/mL) at 48 and 96 hours of ibrutinib treatment (1 μmol/L for JEKO-1, MAVER-1 and MINO and 0.1 μmol/L for SP53) (middle), FACS analysis of apoptotic (Annexin V+/PI+) MCL cells at 96 hours of ibrutinib treatment (right). C, WTS analysis of PIK3IP1 mRNA abundance in serial biopsies of Pt 1 and PBCs. D, q-RT-PCR analysis of relative PIK3IP1 mRNA levels in MCL cells cultured with PD for 72 hours and ibrutinib for 48 hours as indicated. E, live cells (percentage of untreated cells) and cell death (Topro-3+ cells) in MCL cell lines infected with PIK3IP1 shRNA or LacZ shRNA lentivirus and treated with PD and ibrutinib as in D. Error bars represent SD. *, P <0.05, calculated using Student t test. Data are representative of 4 independent experiments.