多西紫杉醇和维甲酸对前列腺癌PC-3细胞的协同作用

目的　观察多西紫杉醇和维甲酸对前列腺癌细胞系 PC- 3的体外体内协同作用 ,并探讨其可能的作用机制。方法　应用光镜形态学 ,四甲基噻唑蓝 (MTT)法 ,流式细胞仪和免疫细胞化学法观察 10 - 6、10 - 7、10 - 8mol/L 多西紫杉醇和 10 - 5、 10 - 6、10 - 7mol/L 维甲酸在体外单药或协同对前列腺癌细胞系 PC- 3的生长抑制作用、诱导凋亡、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多西紫杉醇和维甲酸前后的体质量、肿瘤重量、血清 PSA和肿瘤 PSA免疫组化表达的变化。结果　 10 - 6 mol/L和 10 - 5mol/L维甲酸协同 10 - 7mol/L以上多西紫杉醇作用 4 8h,可增强对前列腺癌 PC- 3细胞的生长抑制作用 (抑制率≥ 6 9.2 % ,P<0 .0 1) ,增强诱导凋亡作用 (凋亡率≥ 2 3.8% ,P<0 .0 5 ) ,下调 Cyclin D1 的表达 (表达率≤ 14 .2 % ) ,与阳性对照组Cyclin D1 表达率 2 5 .5 %相比差异有显著性 (P<0 .0 5 )。维甲酸使多西紫杉醇所致的 G2 /M期细胞比例由 74 .3%变为 5 7.8% ,部分地逆转了其 G2 /M期细胞周期阻滞 (P<0 .0 5 )。协同治疗前后裸鼠体质量无明显变化 ,但肿瘤质量〔(2 .8± 0 .4 ) g〕、血清 PSA〔(4 3± 11) ng/ml〕和肿瘤 PSA免疫组化的表达率〔(2 6± 3.2 ) %〕在协

The Synergistic Effects of Docetaxol and Retinoic Acid on Prostate Cancer Cell Line PC-3

OBJECTIVE: To observe the synergistic effects of docetaxol and retinoic acid on prostate cancer cell line PC-3 in vitro and in vivo. METHODS: Cell morphology, MTT, flow cytometry, immunocytochemical method were used to observe the effects of 10(-6) mol/L, 10(-7) mol/L, 10(-8) mol/L docetaxol and 10(-5) mol/L, 10(-6) mol/L, 10(-7) mol/L retinoic acid on prostate cancer cell line PC-3 in single or synergistic administration ways for 24 and 48 hours in vitro. Male BALB/C-nu mice with PC-3 prostate cancer cell lines were treated by docetaxol and retinoic acid singly or synergistically in vivo. Serum PSA of mice, weights of mice and PSA expression in xenograft tumors of mice by immunohistochemical method were measured. RESULTS: Above 10(-6) mol/L retinoic acid enhanced the growth suppression (suppression ratio > or = 69.2%, P<0.01), apoptosis (Apoptosis ratio > or = 23.8%, P<0.05) and down-regulation of the expression of cyclin D1 (expression ratio < or = 14.2%, P<0.05) induced by above 10(-7) mol/L docetaxol in PC-3 cells. Retinoic acid changed the ratio of G2/M phase induced by docetaxol from 70.3% to 54.6%, and reversed the G2/M arrest partially (P<0.05). Mean serum PSA of mice (43+/-11) ng/ml], weight of xenograft tumors (2.8+/-0.4) g] and PSA expression in tumors (26+/-3.2)%] with PC-3 prostate cancer cell lines of nude mice were decreased significantly in docetaxol combined with retinoic acid group than in control group except weight of mice (20.3+/-1.1) g]. CONCLUSION: Retinoic acid can enhance the growth suppression and apoptosis induced by docetaxol in synergistic way in vitro and in vivo, thus showing their great potential in the treatment of androgen-independent carcinoma of prostate.