Studies On The Effects And Mechanism Of Phe-DDPT On A549 Cells Apoptosis

Objective To observe and discussed the effect of A549 cell line induced by N-(1-O-2,2,6,6-tetramethyl-4-piperidine oxygen carbonyl)-L-phenylalanine 4'-demethyl-4-deoxy podophyllum ester (Phe-DDPT)and Etoposide (VP-16).Results 1. A549cells can be inhibited growing induced by Phe-DDPT, compared 36h OD decreased by Phe-DDPT(p<0.01), inhibited cells growing with VP-16. It is no changes at 24h,48h. At the same time, the effect of Phe-DDPT more usefull than VP-16 (P<0.05, P<0.01).2. Flow cytometry (FCM) measured show A549 cells were arrested in G1 by Phe-DDPT, and most cells were apoptosis. 3. Immunohistochemistry showed pyknosis of nuclei, and appeared fragmentation and apoptotic bodies. After statistical analysis, with drug increased, the same of apoptosis rate.4 DNA fragmentation of A549 cells appeared different sizes, A549 cells have more apoptosis induced by Phe-DDPT.5 Phe-DDPT induced tubulin polymerization condition and generate a large number of microtubule from fluorescence microscopy, and cells number and apoptosis.6 Bax, Caspase3 protein increased and Bcl-2 protein decreased, the expression of show Phe-DDPT maybe play a certain role in cells apoptosis.Conclusions New podophyllotoxin derivatives Phe-DDPT have been inhibited of A549 cells growing. Induced expression of Bax, Caspase, Bcl-2 gene, and arrest cells in G1 times. This effect of inhibitory and low toxicity in anti-tumor compounds taking a important role.