Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol
Autor: | Feng Gu, Guang yuan Zhang, Chun Xiao Lu, Xin Ma, Jin ke Wang, Jun jun Hao, Xiao Ting Gu, Jian Wu, Dong xu He, Zhong yang Ding, Ai qin Mao, Li Fu |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Drug Bridged-Ring Compounds Dicumarol medicine.medical_treatment media_common.quotation_subject Breast Neoplasms Pharmacology 03 medical and health sciences 0302 clinical medicine Breast cancer Mediator Transforming Growth Factor beta Cell Line Tumor Gene expression medicine Humans media_common Chemotherapy business.industry Pregnancy-Specific beta 1-Glycoproteins Cancer Anticoagulants General Medicine medicine.disease 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis PSG1 Female Taxoids business Transforming growth factor |
Zdroj: | Clinical science (London, England : 1979). 130(24) |
ISSN: | 1470-8736 |
Popis: | 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. |
Databáze: | OpenAIRE |
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