Abstract
Background: CD40 is a type α-membrane protein of the tumor necrosis factor receptor super-family, and CD40- induced responses may mediate growth and angiogenesis in carcinoma cells. Objectives: Define the effect of CD40 ligation on AGS gastric cancer cell line and the role of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) signals in this process. Methods: We treated AGS cells with 1 μg/mL soluble CD40 ligand (sCD40L) with or without pre-incubation of either anti-VEGF mAb (MAB293) or VEGFR tyrosine kinase inhibitor (SU5416). We determined the growth effects by cell counts or [3H]-thymidine incorporation assay and VEGF levels in cell-free supernatant using enzymelinked immunosorbent assays. Results: The engagement of CD40-induced AGS cells proliferation accompanied by a significant increase autocrine VEGF through PI3K activation (p <0.05), and exogenous VEGF alone had no effect on spontaneous cell growth. SU5416 with a concentration of 8 μM lead to a dramatic decrease in cell survival induced by sCD40L (p <0.05), whereas MAB293 did not have the similar effect (p >0.05). Conclusion: CD40-CD40L interaction promoted AGS cancer cell line proliferation through a VEGFR-dependent signal pathway in the presence of an internal autocrine loop.
White button, shiitake, and portabella mushrooms inhibit the secretion of vascular endothelial growth factor (VEGF) and the proliferation of the androgen dependent LNCap prostate cancer cell line