机构：[1]Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.[2]Shandong Provincial Key Laboratory of Radiation Oncology , Shandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University Shandong Academy of Medical Sciences , Jinan , China.[3]West China Hospital, Sichuan University and Collaborative Innovation Center , Chengdu , China.四川大学华西医院
Fibrosarcomas are highly aggressive malignant tumors. It is urgently needed to explore targeted drugs and modalities for more effective therapy. Matrix metalloproteinases (MMPs) play important roles in tumor progression and metastasis, while several MMPs are highly expressed in fibrosarcomas. In addition, tissue inhibitor of metalloproteinase 2 (TIMP2) displays specific interaction with MMPs. Therefore, TIMP2 may play an active role in the development of fibrosarcoma-targeting agents. In the current study, a TIMP2-based recombinant protein LT and its enediyne-integrated analog LTE were prepared; furthermore, the fibrosarcoma-binding intensity and antitumor activity were investigated. As shown, intense and selective binding capability of the protein LT to human fibrosarcoma specimens was confirmed by tissue microarray. Moreover, LTE, the enediyne-integrated analog of LT, exerted highly potent cytotoxicity to fibrosarcoma HT1080 cells, induced apoptosis, and caused G2/M arrest. LTE at 0.1 nM markedly suppressed the migration and invasion of HT1080 cells. LTE at tolerated dose of 0.6 mg/kg inhibited the tumor growth of fibrosarcoma xenograft in athymic mice. The study provides evidence that the TIMP2-based reconstituted analog LTE may be useful as a targeted drug for fibrosarcome therapy.
基金：
CAMS Innovation Fund for
Medical Sciences (No. 2016-I2M-3-013), the ‘Significant New Drug
Development’ Major Science and Technology Development Projects of
China (No. 2014ZX09201042-003), and the National Key Research and
Development Program of China (2016YFA0201504).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|2 区医学
小类|1 区药学
最新[2025]版：
大类|2 区医学
小类|1 区药学
第一作者：
第一作者机构：[1]Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
通讯作者：
通讯机构：[1]Institute of Medicinal Biotechnology , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.[*1]Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantanxili, Beijing 100050, China
推荐引用方式(GB/T 7714)：
Xu Jian,Du Yue,Liu Wen-Juan,et al.Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.[J].Drug delivery.2018,25(1):102-111.doi:10.1080/10717544.2017.1410261.
APA：
Xu Jian,Du Yue,Liu Wen-Juan,Li Liang,Li Yi...&Zhen Yong-Su.(2018).Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity..Drug delivery,25,(1)
MLA：
Xu Jian,et al."Intensive fibrosarcoma-binding capability of the reconstituted analog and its antitumor activity.".Drug delivery 25..1(2018):102-111
医学