Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol.

Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analysed the gene expression profiles of preoperative samples from oestrogen receptor (ER)-negative breast cancer patients with different responses to taxane-anthracycline-based (TA-based) chemotherapy, and identified a group of genes that was predictive. Pregnancy specific beta-1-glycoprotein 1 (PSG1) played a central role within signalling pathways of these genes. Inhibiting PSG1 can effectively reduce chemoresistance via a transforming growth factor-β (TGF-β)-related pathway in ER-negative breast cancer cells. Drug screening then identified dicumarol (DCM) to target the PSG1 and inhibit chemoresistance to TA-based chemotherapy in vitro, in vivo, and in clinical samples. Taken together, this study highlights PSG1 as an important mediator of chemoresistance, whose effect could be diminished by DCM. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Citation

Dong-Xu He, Feng Gu, Jian Wu, Xiao-Ting Gu, Chun-Xiao Lu, Ai-Qin Mao, Guang-Yuan Zhang, Zhong-Yang Ding, Jin-Ke Wang, Jun-Jun Hao, Li Fu, Xin Ma. Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol. Clinical science (London, England : 1979). 2016 Dec 01;130(24):2267-2276

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PMID: 27653744

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