Paclitaxel is more effective than thalidomide in inhibiting LNCaP tumor growth in a prostate cancer model

Methods Find Exp Clin Pharmacol. 1998 Nov;20(9):739-42.

Abstract

LNCaP tumors were treated by either administration of paclitaxel, thalidomide or by orchiectomy in order to determine their relationship with markers pertaining to the process of tumor growth, apoptosis or angiogenesis. Forty rats bearing LNCaP tumors were divided into 4 groups of 10 and treated by either paclitaxel (20 mg/kg x 5 days); thalidomide (200 mg/kg x 5 days/week x 5 weeks); or orchiectomy. After 6 weeks serum samples were removed for PSA determination and the animals sacrificed for evaluation of: A) tumor volume; B) tissue bcl-2, cyclin D, PSA and factor VIII immunohistochemically graded (0-5 scale) for marker expression; and C) serum PSA. Comparisons were made to untreated LNCaP tumors. Statistically significant differences were determined using the nonparametric Mann-Whitney test. Paclitaxel produced significant differences in volume (p < 0.001), expression of bcl-2 (p < 0.043), cyclin D (p < 0.023), tissue PSA (p < 0.001) and serum PSA (p < 0.019) levels. Thalidomide altered expression of bcl-2 (p < 0.011) and tissue PSA (p < 0.002). Orchiectomy altered volume (p < 0.002) and bcl-2 expression (p < 0.001). All three therapies have been suggested for prostate cancer and each produced alterations in accepted markers for treatment response (either reduced volume or serum PSA). Paclitaxel significantly influenced the most markers. Of interest was that all treatments, especially thalidomide, a known antiangiogenesis agent, reduced factor VIII, although not significantly. Evidently each treatment evokes different pathways of activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / therapeutic use*
  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Paclitaxel / therapeutic use*
  • Prostatic Neoplasms / drug therapy*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Thalidomide / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins c-bcl-2
  • Thalidomide
  • Paclitaxel