We have examined the antimetastatic effects of taxol on a PC-3 human prostatic tumor variant (PC-3 ML) which metastasizes to the lumbar vertebrae in severe combined immunodeficiency-carrying (SCID) mice. Immunofluorescence labeling indicated that taxol (0.5 to 1.0 µm for 6 h) produced an abnormal bundling of microtubules in a dosage-dependent manner. Slot blotting and gelatinase assays revealed that taxol inhibited secretion of the Mr 72,000 and Mr 92,000 type IV collagenases plus a Mr 57,000 gelatinase. Radioimmunoprecipitation measurements confirmed that the drug inhibited both the secretion and the synthesis of the Mr 72,000 collagenase. Taxol also blocked total protein secretion but did not influence total protein synthesis or turnover. Boyden chamber chemotactic studies further showed that taxol (0.5 to 1.0 µm) inhibited invasion of Matrigel. More importantly, studies in SCID mice demonstrated that taxol (50 to 250 mg/m2/day) blocked the establishment, growth, and long-term survival of PC-3 ML cells.
This study was supported by NIH-NCI Grant CA53518 to M. E. S.