紫杉醇和吉西他滨对激素非依赖性前列腺癌的作用

目的 观察紫杉醇(PA)协同吉西他滨(GE)对前列腺癌细胞系PC-3的体内外作用,并探讨其可能的作用机制。方法 应用光镜形态学、噻唑蓝(MTT)法、流式细胞仪和免疫细胞化学法观察了10^-6、10^-7、10^-8 mol/L浓度PA和10^-7、10^-8、10-9 mol/L浓度GE在体外单药或协同对前列腺癌细胞系PC-3的作用、对细胞DNA含量及cyclin D1表达的影响。观察PC-3细胞荷瘤裸鼠单独及协同使用PA和GE前后的体质量、肿瘤质量、血清PSA和肿瘤PSA免疫组化的变化。结果 10^-8 mol/L以上浓度GE作用48 h,可增强10^-7 mol/L以上浓度PA对前列腺癌PC-3细胞系的生长抑制[抑制率≥(50.8±4.2)%,P<0.05],增强诱导凋亡作用[凋亡率≥(22.9±2.3)%,P<0.05],下调Cyclin D1的表达[表达率≤(9.6±1.6)%],与阳性对照组cyclin D1表达率(25.5±4.1)%相比差异有显著性(P<0.01)。GE使PA所致的G₂/M期细胞周期阻滞比例由(70.3±9.7)%减至(38.2±4.2)%,部分地逆转了其G₂/M期细胞周期阻滞(P<0.01)。协同治疗前后裸鼠体质量无明显变化,但肿瘤质量(3.2.±0.5 g)、血清PSA[(51±14) ng/ml]和肿瘤PSA免疫组化的表达率[(30±3.7)%]在协同治疗组显著低于其他组(P<0.05或0.01)。结论 PA和GE可以在体内外协同增强对前列腺癌细胞系PC-3的生长抑制和诱导凋亡作用,显示了PA和GE协同用于治疗激素非依赖性前列腺癌的可能性,并部分地解释了其作用机制。

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, 1×10^-7 mol/L and 1×10^-8 mol/L PA and 1×10^-7 mol/L, 1×10^-8 mol/L and 1×10-9 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 1×10^-8 mol/L significantly enhanced the effect of PA above 1×10^-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 G₂/M phase from 70.3%±9.7% to 38.2%±4.2%, and partially reversed the G₂/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.