Anti-DLL4 monoclonal antibody, clone MHD4-46

Background: Activation of Notch signaling was found to be associated with cancer. Gambogic acid (GA) was reported to be an anti-cancer agent. This study investigated the anti-cancer effect of GA on human non-small cell lung cancer (NSCLC) cells. Involvement of the Notch pathway was also studied. Matreial/Methods: GA at 0, 0.5, 0.75, and 1.0 mu mol/l was used to incubate A549 and SPC-A1 cells. MTT assay was used to deter- mine the cell viability. TUNEL assay was used to detect the apoptosis. Western blotting was used to evaluate protein expression levels, protein phosphorylation levels, and nuclear translocation levels. Results: Notch signaling pathway was activated in NSCLC cells. GA treatment significantly inhibited NSCLC cell viability and increased cell apoptosis. GA treatment significantly decreased the expression levels of DLL1, DLL3, DLL4, Jagged1, Jagged2, Bcl2, and PK3K, inhibited NICD nuclear translocation and Akt phosphorylation, and increased expression level of active caspase3. Conclusions: GA inhibited NSCLC cell viability by inducing apoptosis. Inhibition of the Notch signaling pathway was the mechanism involved in the anti-proliferation effect of GA on NSCLC.

Resveratrol (Res) has an anti-tumor effect. Notch signaling components from breast cancer cells treated in culture with Resveratrol was investigated. MDA-MB-231cells were divided into control group (Res-untreated) and Res-treated groups including six concentrations 0 mu M, 10 mu M, 20 mu M, 40 mu M, 80 mu M and 160 mu M. Cytotoxicity test were evaluated by CCK-8. The mRNA and Protein expression levels of Notch1, Jagged1, Dll4 and Hes-5 were detected by RT-PCR and Western blot. The mRNA expression of Notch1, Jagged1, Hes-5 and Dll4 in the Res administration group decreased significantly (0.01 < p < .05), and Hes-5 and Dll4 were extremely significant (p < .01). Compared with the blank control group, the protein expression of Notch1 and Dll4 decreased significantly in each concentration Res group, but the decrease of protein expression of Jagged1 and Hes-5 was not significant. In conclusion, Res regulates mRNA and protein expression of Notch1, Dll4 of MDAMB-231 cells via Notch pathway.