Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice.
The combined influence of alendronate, a bisphosphonate compound, and taxol on the establishment and growth of human PC-3 ML subclones injected intravenously via the tail vein in SCID mice was investigated. The pretreatment of SCID mice with alendronate (0.04-0.1 mg/kg twice weekly or 0.1 mg/kg weekly) partially blocked the establishment of bone metastases by human PC-3 ML cells and resulted in tumor formation in the peritoneum and other soft tissues. However, alendronate pretreatment of mice (0.1 mg/kg twice weekly or weekly) and dosing along with taxol (10-50 mg/kg/day, twice weekly, or weekly) blocked the growth of PC-3 ML tumors in the bone marrow and soft tissues in a statistically significant manner and improved survival rates significantly (p < 0.001) by 4-5 weeks. ELISAs and zymography of matrix metalloproteinase production in vitro and in vivo showed that alendronate and taxol alone partially inhibited metalloproteinase production, but that taxol in combination with alendronate totally blocked protease production and release. The combined activities of alendronate and taxol appeared to inhibit the establishment and growth of tumors in SCID mice, perhaps, in part, as a result of inhibition of protease production and release.
Stearns
M E
ME
Department of Pathology, Medical Colleges of Pennsylvania, Allegheny University of Health Sciences, Philadelphia 19102, USA.
Wang
M
M
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D008666:Metalloendopeptidases; D017239:Paclitaxel; D019386:Alendronate