Taxol blocks processes essential for prostate tumor cell (PC-3 ML) invasion and metastases.
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 microM 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 M(r) 72,000 and M(r) 92,000 type IV collagenases plus a M(r) 57,000 gelatinase. Radioimmunoprecipitation measurements confirmed that the drug inhibited both the secretion and the synthesis of the M(r) 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 microM) 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.
Department of Pathology, Medical College of Pennsylvania, Philadelphia 19129.
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D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002465:Cell Movement; D018093:Gelatinases; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D003012:Microbial Collagenase / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017239:Paclitaxel; D010434:Pepsin A / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D011506:Proteins / Q000378:metabolism
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D011506:Proteins; D010434:Pepsin A; D018093:Gelatinases; D003012:Microbial Collagenase; D017239:Paclitaxel