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 into monolayer cultures or multicellular tumor spheroids of human non-small 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 with 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 destruction of the tumors. These results support the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.
Fujiwara
T
T
Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Grimm
E A
EA
Mukhopadhyay
T
T
Zhang
W W
WW
Owen-Schaub
L B
LB
Roth
J A
JA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000628:therapy; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D002945:Cisplatin