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A Retroviral Wild-type p53 Expression Vector Penetrates Human Lung Cancer Spheroids and Inhibits Growth by Inducing Apoptosis¹

The Departments of Thoracic and Cardiovascular Surgery [T. F., T. M., D. W. C., J. A. R.], Tumor Biology [E. A. G., J. A. R.], General Surgery [E. A. G.], and Immunology [L. B. O-S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

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 multi-cellular 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.

¹ Partially supported by grants from the National Cancer Institute and NIH (RO1 CA45187) (J. A. R.) and (RO1 CA45225) (E. A. G.), by National Cancer Institute of Training Grant (CA09611-01) (J. A. R.), by gifts to the Division of Surgery from Tenneco and Exxon for the Core Lab Facility, by the M. D. Anderson Cancer Center Core Grant (NCI CA16672), and by a grant from the Mathers Foundation (J. A. R.).

² To whom requests for reprints should be addressed.

Received 6/11/93. Accepted 8/ 4/93.

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