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BRD4 inhibitor JQ1 increase the sensitivity of arsenic trioxide in pancreatic cancer

ABSTRACT: Pancreatic cancer is a deadliest type of malignancy, largely due to lack of effective intervention. We here report a pair of agents, ATO and JQ1, which synergistically induce apoptosis in the malignancy. Through global and molecular approaches, we have provided evidence that these agents are both able to modulate ER stress and autophagy in the cancer, probably acting in different ways. Cross-talks between ER stress and autophagy are implicated during ATO/ATO plus JQ1 induced apoptosis, in which NRF2 appears to play a central role. of the globe transcriptional profiles of ATO regulated genes in breast, colon and lung cancer cells with different p53 status. We find p53 wild type cells are resistant to ATO induced globe dynamic transcriptional changes, thus resistant to ATO induced cell growth inhibition. P53 inhibitor PFTα releases p53 mediated transcriptional resistance and increases the sensitivity of ATO in p53 wild type tumor cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124069 | GEO | 2019/12/31

REPOSITORIES: GEO

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