Transcriptomics

Dataset Information

6

Transcription profiling by array of H. sapeins NSCLC A549 cell line to investigate two distinct poly(ADP-ribose) polymerase (PARP) inhibitors as a hyperadditive combination effect with CDDP


ABSTRACT: Non-small cell lung cancer (NSCLC) is often treated with cisplatin (CDDP). Here, we report that two distinct poly(ADP-ribose) polymerase (PARP) inhibitors exhibited a hyperadditive combination effect with CDDP to kill NSCLC cells. A majority of CDDP-resistant cell lines and clones exhibited constitutively increased PARP expression and enzymatic activity. Cells with hyperactivated PARP initiated a DNA damage response and the intrinsic pathway of apoptosis in response to pharmacological PARP inhibition or PARP1-targeting siRNAs. Transcriptome analysis depicted an unsupervised hierarchical clustering of NSCLC cells and CDDP resistant counterparts regarding to their response to PARP inhibitors. PARP-overexpressing tumors displayed elevated levels of intracellular poly(ADP-ribose) (PAR), which predicted the response to PARP inhibitors in vitro and in vivo more accurately than PARP expression itself. Thus, CDDP-resistant cancer cells develop a dependency to PARP, becoming susceptible to PARP inhibitor-induced apoptosis.

ORGANISM(S): Homo sapiens  

SUBMITTER: justine JG guegan   

PROVIDER: E-MTAB-1353 | ArrayExpress | 2012-11-12

REPOSITORIES: ArrayExpress

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