A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis.
Multicellular tumor spheroids approximate the three-dimensional configuration of primary and metastatic tumors. The effects of retrovirus-mediated transduction of wild-type p53 (wt-p53) were studied on multicellular tumor spheroids of human non-small cell lung cancer cell lines H322a, the p53 gene of which is homozygously mutated at codon 248, and WT226b, which has endogenous wt-p53. The growth of WT226b spheroids was not affected by exogenous wt-p53 transduction; the growth of H322a spheroids, however, was significantly inhibited by the addition of wt-p53 virus stocks. Transduction of cells by the wt-p53 retroviral vector and penetration of multiple cell layers in H322a spheroids was demonstrated by in situ polymerase chain reaction/hybridization with the neomycin-resistant neo probe. Apoptotic changes indicating programmed cell death were observed in H322a spheroids treated with the wt-p53 virus. These results suggest that retroviral vectors can penetrate into multiple cell layers of three-dimensional tumor masses and induce potentially therapeutic effects.
Department of Thoracic and Cardiovascular Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
T
T
Fujiwara
E A
EA
Grimm
T
T
Mukhopadhyay
D W
DW
Cai
L B
LB
Owen-Schaub
J A
JA
Roth
D017209:Apoptosis; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D004247:DNA / Q000378:metabolism; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D008969:Molecular Sequence Data; D012190:Retroviridae / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004247:DNA