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. Author manuscript; available in PMC: 2013 Jan 1.
Published in final edited form as: Cancer Res. 2011 Nov 11;72(1):294–303. doi: 10.1158/0008-5472.CAN-11-3240

Fig. 6. Tumor growth in vivo is inhibited by combination treatment of ABT-737 and SMI-4a.

Fig. 6

A, Mice were subcutaneously inoculated with LNCaP cells. Tumor volume was monitored during the following treatments: vehicle (V), ABT-737 (ABT; 50 mg/kg; i.p., QD), SMI-4a (4a; 60 mg/kg, oral gavage, BID) or a combination of SMI-4a and ABT-737 (ABT plus 4a) for 16 days (mean ± SEM). B, Immunohistochemical analysis of Mcl-1, cleaved caspase-3 (casp-3) and H&E staining. C, Western blot analysis of Noxa, Mcl-1, cleaved casp-3, β-actin, and GAPDH. Five representative tumors for each treatment were examined. D, qT-PCR analysis of XBP-1 splicing in subcutaneous tumors of treatment groups. Five representative tumors for each treatment group are shown. E, Proposed mechanistic model by which Pim inhibitor synergizes with ABT-737 to induce apoptosis. Pim inhibitors reduce Mcl-1 protein translation through activation of AMPK to block the mTORC1-mediated 5’cap-dependent protein translation. In addition, this treatment activates the UPR signaling to induce Noxa, thereby promoting increased Mcl-1 turnover.