Fig. 3: In p53+ DLBCL, combined chidamide and duvelisib induce apoptosis by suppressing autophagy. | Cell Death Discovery

Fig. 3: In p53+ DLBCL, combined chidamide and duvelisib induce apoptosis by suppressing autophagy.

From: Combination of HDAC inhibitor and PI3K inhibitor suppresses autophagy and induces apoptosis via cytoplasmic IκBα stabilization in p53-mutant diffuse large B-cell lymphoma

Fig. 3

Tumor specimens from 6 DLBCL cases with p53-mutant and 6 cases with p53-wild-type were collected. RNA-seq was performed to profile transcriptomes, followed by gene set enrichment analysis (GSEA) for identifying signaling pathway alterations (A). DB cells were exposed to specified concentrations of chidamide, duvelisib, or their combination for 24 hours, followed by RNA sequencing. DEGs were screened (B, C) and subjected to enrichment analysis (D). Western blotting was performed to detect the expression of the autophagy-related protein Beclin1 in TMD8, Toledo, and DB cells post-treatment (E). Immunofluorescence was utilized to assess expression levels of the autophagic marker LC3 (F). TEM was employed to examine alterations in autolysosomes following drug treatment (G). A DB-Beclin1-overexpressing cell line was constructed for further validation, wherein the apoptosis process originally promoted by combination therapy was partially rescued in Beclin1-overexpressing cells (H, I). The GEPIA database was analyzed to evaluate the prognostic relationship between LC3 expression and survival outcomes in DLBCL patients (J). In cell-based assays and western blotting, DMSO served as the vehicle control, diluted in culture medium to a final concentration of 0.05% (v/v).

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