SY-707,an ALK/FAK/IGF1R inhibitor,suppresses growth and metastasis of breast cancer cells  

作　　者：Ping Liu Yinghui Sun Shuang Liu Jing Niu Xijie Liu Qiaoyun Chu 

机构地区：[1]Department of Geriatrics,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200092,China [2]Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China [3]Shouyao Holdings Co.,Ltd,Beijing 100195,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第2期252-260,共9页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Twelfth Five-year Plan Periods(Nos.2012ZX09401007 and 2015ZX09101001).

摘　　要：Focal adhesion kinase(FAK),a multi-functional cytoplasmic tyrosine kinase,plays a critical role in cancer migration,proliferation and metastasis via regulating multiple signaling pathways.SY-707 is an anaplastic lymphoma kinase(ALK)/FAK/type 1 insulin-like growth factor receptor(IGF1R)multi-kinase inhibitor which is now being evaluated in phase II clinical trials for ALK positive non-small cell lung cancer(NSCLC).However,the effect of SY-707 on breast cancer is unknown.In this study,we assessed preclinical the anti-growth and anti-metastasis potency of SY-707 in breast cancer cells.ATP content,PE-Annexin V,and would healing assays were used to examine cell proliferation,cell cycle and migration.Then,SD rat and beagle dog models were used to evaluate the pharmacokinetics profile of SY-707,and mouse xenograft model was used to evaluate the anti-cancer activities of SY-707 in vivo.We found that breast cancer cells apoptosis were induced by SY-707.Moreover,SY-707 exerted inhibition on cell migration and adhesion in a dose-dependent manner.In T47D xenograft mice,SY-707 had significant anti-tumor activities alone or synergistically with Paclitaxel.Meanwhile,SY-707 also displayed significant suppression on spontaneous metastasis of tumor to the lung in 4T1 murine breast cancer xenograft model.In conclusion,SY-707 has potent antiproliferation and anti-migration potential in breast cancer in vitro and in vivo,implying its therapeutic application for the treatment of breast cancer in future clinical trials.

关 键 词：SY-707 ANTI-TUMOR ANTI-METASTASIS breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]