Abstract C51: Chemosensitisation to cisplatin by STAT3 inhibitors is mediated through the inhibition of DNA interstrand crosslink unhooking

Signal Transducer and Activator of Transcription 3 (STAT3) is constitutively activated in many cancer cell lines, leading to survival, proliferation, angiogenesis and metastasis. The inhibition of STAT3 by natural or synthetic compounds has been shown to sensitise cancer cell lines to the chemothera...

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Published in:Molecular cancer therapeutics 2015-12, Vol.14 (12_Supplement_2), p.C51-C51
Main Authors: Valentine, Helen, Dixon, Emily, Hartley, John A., Kiakos, Konstantinos
Format: Article
Language:English
Online Access:Get full text
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Summary:Signal Transducer and Activator of Transcription 3 (STAT3) is constitutively activated in many cancer cell lines, leading to survival, proliferation, angiogenesis and metastasis. The inhibition of STAT3 by natural or synthetic compounds has been shown to sensitise cancer cell lines to the chemotherapy agent cisplatin, however the molecular mechanisms contributing to this chemosensitisation have not yet been fully elucidated. Therefore we investigated the effect of STAT3 inhibition on cisplatin-induced DNA damage and key DNA repair factors. STAT3 inhibitors stattic and curcumin were investigated in combination with cisplatin using the Suphorhodamine B cell growth inhibition assay in the DU145 prostate cancer and A549 non-small cell lung cancer cell lines. Combination treatments result in a significant (P
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.TARG-15-C51