INDUCTION OF CHEMOSENSITIVITY IN HUMAN LUNG-CANCER CELLS IN-VIVO BY ADENOVIRUS-MEDIATED TRANSFER OF THE WILD-TYPE P53 GENE

Recombinant adenovirus-mediated transfer of the wild-type p53 gene int o monolayer cultures or multicellular tumor spheroids of human nonsmal l cell lung cancer cell line H358, which has a homozygous deletion of p53, markedly increased the cellular sensitivity of these cells to the chemotherapeutic drug cisplatin. Treated cells underwent apoptosis wi th specific DNA fragmentation. Direct injection of the p53-adenovirus construct into H358 tumors s.c. implanted into nu/nu mice, followed by i.p. administration of cisplatin, induced massive apoptotic destructi on of the tumors. These results support the clinical application of a regimen combining gene replacement using replication-deficient wild-ty pe p53 adenovirus and DNA-damaging drugs for treatment of human cancer .