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Figure 5 | Journal of Hematology & Oncology

Figure 5

From: Histone deacetylase inhibitor potentiated the ability of MTOR inhibitor to induce autophagic cell death in Burkitt leukemia/lymphoma

Figure 5

Valproic acid overcame temsirolimus-mediated AKT activation via HDAC3 inhibition. (A) Valproic acid (VPA), either alone or in combination, inhibited HDAC3 expression (upper panel), in parallel with decreased HDAC3 enzymatic activity (lower panel) and p-AKT expression (upper panel). (B) Compared with the negative control (CON siRNA), VPA failed to alter p-AKT expression in Namalwa cells transfected with HDAC3 siRNA. (C and D) Tumor cell growth inhibition (C, *P<0.05 comparing with CON siRNA) and autophagic cell death (D, as detected by immunefluorescence study on BECN1 and P62) were less affected by VPA in Namalwa cells transfected with HDAC3 siRNA than in those transfected with CON siRNA. (E) In MYC-expressing diffuse large B-cell lymphoma cell line DB, characteristic changes of autophagy were more frequently detected by ultrastructural study in the combination group than in the single agent group. (F) VPA (0.5 mM) combined with temsirolimus (TEM, 1 nM) significantly increased CDKN1A and CDKN1B, decreased p-AKT, p-MTOR and MYC oncoprotein.

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