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Fig. 6 | Cancer Cell International

Fig. 6

From: HDACs/mTOR inhibitor synergizes with pyrotinib in HER2-positive pancreatic cancer through degradation of mutant P53

Fig. 6

HDAC inhibition mediates the degradation of mutant P53 to promote apoptosis together with HER2 and mTOR inhibition in PDAC. A–D Cells were treated with DMSO or pyrotinib of 1 μM or HDAC inhibitor (SAHA of 2 μM, Panobinastat of 5 nM) or mTOR inhibitors (Rapamycin of 15 μM, Everolimus of 20 μM) or combined. Cell viability was assessed by CCK8. E Heatmap of gene expression values in AsPC-1 and PATU 8988-T treated with pyrotinib versus DMSO for 24 h. F Top 10 of enrichment score for selected GO functional catagories of top 10% differential expressed genes in AsPC-1 and PATU 8988-T. G Validation of P53 by quantitative PCR analysis in AsPC-1 and PATU 8988-T. H Downstream BAI1, P21 and PUMA analysed by quantitative PCR analysis in AsPC-1 and PATU 8988-T. I Immunoblo analysis of the HER2, pHER2, mTOR, pmTOR, HDAC1, HDAC6 as direct targets of combination therapy and acetylation of P53 and H3 as well as P53 and its downstream MDM2 Bcl2 and pBcl2 and Bim in AsPC-1 and PATU 8988-T cells treated with DMSO, monotherapy or combination therapy. Data are represented as mean ± SD. Statistical significance was assessed using a Student t test. *P < 0.05, **P < 0.01, ***P < 0.001. ns, not significant

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