ANTITUMOR-ACTIVITY OF BAX AND P53 NAKED GENE-TRANSFER IN LUNG-CANCER - IN-VITRO AND IN-VIVO ANALYSIS

In vitro and in vivo data have demonstrated that virus-mediated p53 ge ne transfer can induce active cell death and lung tumor regression. In contrast, the therapeutic potential of bar, another apoptosis-inducin g gene, has not been described. We compared p53 and bar cytotoxic effe cts by transient transfection of an average of 25 +/- 5% of the H-322 and H-358 bronchioloalveolar carcinoma cell lines in vitro, Under thes e conditions, box expression killed 70 to 90% of the transfected cells whereas p53 killed only 40% of them. The killing activity of both gen es involved apoptosis, as shown by TUNEL staining. Surprisingly, BrdU incorporation indicated that the cells that did resist Bar toxicity we re blocked in the pre-S phase of the cell cycle, a result expected for p53 only. In vivo, repeated injections of naked DNA encoding Bar or p 53 inhibited the growth of 4-mm preestablished H-322 tumors in nude mi ce. Growth retardation only, and not inhibition, was observed in H-358 , a poorly transfectable and rapidly growing tumor. These results indi cate that Bar and p53 share a similar, strong antitumor activity in vi vo, even if the former is a more potent inducer of apoptosis in vitro.