Abstract 3610: DMH4, A VEGFR2 inhibitor effectively suppresses proliferation and migration of lung cancer cells

Abstract

Abstract Background Currently there is a major unmet medical need for effective therapy of the non-small cell lung cancer (NSCLC). It is well known that vascular endothelial growth factor (VEGF) signaling plays a critical role in regulating tumor angiogenesis, and bevacizumab is the only approved antiangiogenic agent for the treatment of NSCLC to date. Due to individual differences in drug response, developing novel angiogenic inhibitors is essential for NSCLC treatment. We have recently developed DMH4, a small molecule which specifically inhibits VEGF signaling by targeting VEGF receptor 2 (VEGFR2) (Hao, et al 2010). Here, we show that DMH4 can effectively suppress proliferation and migration of NSCLC cells. Method Briefly, NSCLC cell line H460, A549 and a lung fibroblast cell line MRC5 was treated by DMH4 at concentrations of 0.25 ug/ml, 0.5 ug/ml,1 ug/ml, 2 ug/ml, 4 ug/ml, 8 ug/ml and 16 ug/ml. MTT assay was taken out for testing cell viability at 24 hr, 48 hr and 72 hr. Meanwhile, FITC Annexin V/PI double staining was taken out to distinguish apoptosis and necrosis. Scratch assay was taken out to evaluate cell migration. Cell lysate was collected at the same time. Phospho-VEGF Receptor 2 level and Phospho-Akt level were tested through Western Blot. 43 apoptosis related protein levels were measured using human apoptosis antibody array assay. Result The data from MTT assay showed that DMH4 treatment decreased cell viability in a dose-depend manner. At the concentrations of 1 ug/ml, DMH4 effectively decreased viabilities of both H460 (82.1%, P<0.01) and A549 (78.5%, P<0.01) NSCLC cells, but had no effect on the normal lung MRC5 cells (103.6%). In addition, our study demonstrated that DMH4 promoted apoptosis in NSCLC cells, but did not show significantly effects in normal lung cells. Our further study indicated that DMH4 also suppressed NSCLC migration. Through Western Blot, phospho-VEGFR2 and phosphor-Akt levels were both detected lower in H460 and A549 than in MRC5. Conclusion As it can effectively suppress cell proliferation and migration in NSCLC cells but not in normal lung cells, DMH4 may be a good drug lead as a new VEGFR2 inhibitor for NSCLC treatment in the future. Note: This abstract was not presented at the meeting. Citation Format: Hao Li, Chay Bae, Nicky Gazy, Jijun Hao, Li Zhong. DMH4, A VEGFR2 inhibitor effectively suppresses proliferation and migration of lung cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3610. doi:10.1158/1538-7445.AM2015-3610