J Appl Biomed 16:46-50, 2018 | DOI: 10.1016/j.jab.2017.10.006

DMH4, a VEGFR2 inhibitor, effectively suppresses growth and invasion of lung cancer cells

Hao Li^a,b, Helen L. Ha^a, Xiaoxu Ding^c, Chay Bae^a, Nicky Gazy^a, Jijun Hao^d,*, Li Zhong^a,b,*

^a Hebei University, College of Life Sciences, Department of Cell Biology, Baoding, Hebei, China

^b Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Department of Basic Medical Sciences, Pomona, CA, USA

^c Affiliated Hospital of Hebei University, Baoding, Hebei, China

^d Western University of Health Sciences, College of Veterinary Medicine, Pomona, CA, USA

Non-small-cell lung cancer (NSCLC), the most common type of lung cancer, remains the leading cause of cancer death worldwide. Blocking vascular endothelial growth factor (VEGF) signalling is an effective approach to the treatment of NSCLC. Small molecules have been proven to be good resource for discovery of inhibitors of VEGF signalling. DMH4 is a small molecule that we previously developed and demonstrated to have the property of selectively inhibiting VEGF signalling by targeting VEGF receptor 2 (VEGFR2). In this study, we reported that DMH4 can effectively block phosphorylation of VEGFR2 in both H460 and A549 NSCLC cells, which resulted in significant reduction of NSCLC cell viability in a dose-dependent manner, and the growth inhibition (GI50) of DMH4 against H460 and A549 cell lines were 13.27 and 2.75 mm respectively at 24 h. Our further studies demonstrated that DMH4 significantly suppressed migration and invasion of A549 and H460 cells, and induced apoptosis in those cells. Therefore, DMH4 as a small molecular VEGFR2 inhibitor may represent a new valuable drug lead for NSCLC treatment.

Keywords: DMH4; Lung cancer; Antiangiogenic; Small molecules; VEGF; VEGFR2

Received: February 1, 2017; Revised: September 5, 2017; Accepted: October 16, 2017; Published: February 1, 2018  Show citation