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  • Title: A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis.
    Author: Fujiwara T, Grimm EA, Mukhopadhyay T, Cai DW, Owen-Schaub LB, Roth JA.
    Journal: Cancer Res; 1993 Sep 15; 53(18):4129-33. PubMed ID: 8395976.
    Abstract:
    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.
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