pLXSN-Tum-5 inducing HUVEC apoptosis through mitochondrial pathway

Formation of vessels is a key regulator for the growth of solid tumor. So, angiogenesis inhibitors are very important for the cancer therapy. Tumstatin is a 28 kDa cryptic domain shed from the carboxy terminal region of a3 chain type IV collagen by matrix metalloproteases. Tumstatin can inhibit tumor growth in mice by inducing the apoptosis in endothelial cells. But, it is indefinite that whether Tum-5 can induce human endothelial cells apoptosis. Based on the isolation of the coding sequence of human Tum-5 and constructing it into plasmid pLXSN, We investigated the apoptosis induced by Tum-5 and the mechanism by the transfect of retroviral packing Tum-5 gene into cultured HUVEC. The results illuminated that Tum-5 significantly inhibited HUVEC cell proliferation in a titer dependent model, and Tum-5 can also induced human EC apoptosis. The translation and transcription of Bax were up-regulated Bcl-2 was down-regulated, and followed the rising of Bax/Bcl-2 ratio the caspase-3 over expression. In conclusion, Tum-5 may induce HUVEC apoptosis through a mitochondrial pathway.