[Synergistic effects of paclitaxel and gemcitabine on androgen-independent prostate cancer].

Objective: To observe the synergistic effects of paclitaxel (PA) and gemcitabine (GE) in vitro and in vivo on prostate cancer cell line PC-3.

Methods: Cell morphological observation, MTT assay, flow cytometry, and immunocytochemical method were used to observe the effects of 1+/-10(-6) mol/L, 1 x 10(-7) mol/L and 1 x 10(-8) mol/L PA and 1 x 10(-7) mol/L, 1 x 10(-8) mol/L and 1 x 10(-9) mol/L GE on prostate cancer cell line PC-3 in vitro in a single or combined administration for 48 h. Male BALB/C-nu mice bearing PC-3 prostate cancer were treated with docetaxol and retinoic acid singly or synergistically, followed by measurement of the body weight and immunohistochemical examination of serum prostate specific antigen (PSA) and PSA expression in the implanted tumors.

Results: GE at the concentration of 1 x 10(-8) mol/L significantly enhanced the effect of PA above 1 x 10(-7) mol/L in inducing growth inhibition (with an inhibition rate over 50.8%+/-4.2%, P<0.05) and apoptosis (apoptosis rate over 22.9%+/-2.3%, P<0.05) of PC-3 cells and in down-regulating the expression of cyclin D1 (expression rate no higher than 9.6%+/-1.6%, P<0.01) in PC-3 cells. GE lowered the rate of PA-induced cell cycle arrest at G(2)/M phase from 70.3%+/-9.7% to 38.2%+/-4.2%, and partially reversed the G(2)/M arrest (P<0.01). Synergistic treatment of the tumor-bearing mice caused little change in the body weight, but the serum PSA (51+/-14 ng/ml), implanted tumor mass (3.2+/-0.5 g) and PSA expression in the tumors (30%+/-3.7%) were all decreased significantly in comparison with the control mice (21.6+/-1.7 g).

Conclusions: GE can enhance PA-induced tumor cell growth suppression and apoptosis in a synergistic manner both in vitro and in vivo, suggesting their great potential in clinical treatment of androgen-independent prostate cancer.