We previously reported that supplementation of a cationic
liposome with
transferrin (Tf) greatly enhanced lipofection efficiency (P.-W. Cheng, Hum. Gene Ther. 1996;7:275-282). In this study, we examined the efficacy of p53 and PTEN tumor suppressor gene
therapy in a mouse xenograft model of human prostate PC-3
carcinoma cells, using a vector consisting of dimyristoyloxypropyl-3-dimethylhydroxyethyl
ammonium bromide (
DMRIE)-
cholesterol (DC) and Tf. When the volume of the
tumors grown subcutaneously in athymic nude mice reached 50-60 mm(3), three intratumoral
injections of the following four formulations were performed during week 1 and then during week 3: (1) saline, (2) DC + Tf + pCMVlacZ, (3) DC + Tf + pCMVPTEN, and (4) DC + Tf + pCMVp53 (standard formulation). There was no significant difference in
tumor volume and survival between group 1 and group 2 animals. As compared with group 1 controls, group 3 animals had slower
tumor growth during the first 3 weeks but thereafter their
tumor growth rate was similar to that of the controls. By day 2 posttreatment, group 4 animals had significantly lower
tumor volume relative to initial
tumor volume as well as controls at the comparable time point. Also, animals treated with p53 survived longer. Treatment with DC, Tf, pCMVp53, DC + pCMVp53, or Tf + pCMVp53 had no effect on
tumor volume or survival. Expression of p53
protein and apoptosis were detected in
tumors treated with the standard formulation, thus associating p53
protein expression and apoptosis with efficacy. However, p53
protein was expressed in only a fraction of the
tumor cells, suggesting a role for bystander effects in the efficacy of p53 gene
therapy. We conclude that intratumoral gene delivery by a nonviral vector consisting of a cationic
liposome and Tf can achieve efficacious p53 gene
therapy of
prostate cancer.