2. Academic Validation
  3. Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo

Novel ADAM-17 inhibitor ZLDI-8 inhibits the proliferation and metastasis of chemo-resistant non-small-cell lung cancer by reversing Notch and epithelial mesenchymal transition in vitro and in vivo

  • Pharmacol Res. 2019 Oct;148:104406. doi: 10.1016/j.phrs.2019.104406.
Hong-Yuan Lu 1,  Yu-Xin Zu 2,  Xiao-Wen Jiang 2,  Xiao-Tong Sun 2,  Tian-Yi Liu 2,  Ruo-Lan Li 2,  Qiong Wu 2,  Ying-Shi Zhang 3,  Qing-Chun Zhao 4
Affiliations

Affiliations

  • 1 Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, China.
  • 2 Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: zhangyingshi526@163.com.
  • 4 Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, China. Electronic address: zhaoqingchun1967@163.com.
PMID: 31442576 DOI: 10.1016/j.phrs.2019.104406
Abstract

Acquired drug-resistant non-small cell lung Cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving Enzyme ADAM-17 we found before. However, the effects of ZLDI-8 on resistant NSCLC was unclear. Here, we demonstrated for the first time that ZLDI-8 could induce Apoptosis in lung Cancer, especially in chemotherapy-resistant non-small cell lung Cancer cells, and also inhibit migration, invasion and EMT phenotype of drug-resistant lung Cancer. ZLDI-8 inhibits the Notch signaling pathway, thereby regulating the expression of survival/Apoptosis and EMT-related proteins. Moreover, ZLDI-8 suppresses multidrug-resistant lung Cancer xenograft growth in vivo and blocks metastasis in a tail vein injection mice model. Therefore, ZLDI-8 is expected to be an effective agent in the treatment of drug-resistant lung Cancer.

Keywords

Apoptosis; Metastasis; NSCLC; Notch; Resistant; ZLDI-8.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15860
    99.90%, Notch Inhibitor