多西紫杉醇对激素非依赖性前列腺癌的体内外作用研究

The effect of docetaxol on androgen-independent prostate cancer in vitro and in vivo

目的 观察多西紫杉醇对激素非依赖性前列腺癌细胞系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、MTT法、流式细胞仪和免疫细胞化学法观察了10-6mol/L、10-7mol/L、10-8mol/L浓度多西紫杉醇在体外对前列腺癌细胞系PC-3的作用和对细胞DNA含量及Cyclin D1表达的影响。观察PC-3细胞荷瘤裸鼠使用20mg/kg多西紫杉醇治疗前后的体重、肿瘤重量、血清PSA和肿瘤PSA免疫组化的变化。结果 10-7mol/L以上浓度多西紫杉醇对前列腺癌细胞系PC-3有明显的生长抑制作用(抑制率≥47.5%,P<0.05),增强诱导凋亡作用(凋亡率≥16.8%,P<0.01),下调Cyclin D1的表达(表达率≤10.8%),与阳性对照组Cyclin D1表达率25.5%相比有显著差异(P<0.05)。治疗前后裸鼠体重无明显变化,但肿瘤重量(3.70.4)g、血清PSA(9513)ng/ml和肿瘤PSA免疫组化的表达率(66.03.8)%在治疗组显著低于对照组(P<0.05或0.01)。结论 多西紫杉醇对激素非依赖性前列腺癌细胞系PC-3及荷瘤鼠肿瘤均有明显的生长抑制和诱导凋亡作用,显示了多西紫杉醇用于治疗激素非依赖性前列腺癌的可能性和价值。

Objective To observe the effect of docetaxol on androgen-independent prostate cancer cell line PC-3 in vitro and in vivo. Methods Cell morphology, MTT, flow cytometer, immunocytochemical method were used toobserve the effect of 10-6mol/L、10-7mol/L、10-8mol/L docetaxol on prostate cancer cell line PC-3 in vitro. MaleBALB/C-nu mice with PC-3 prostate cancer cell lines were treated by docetaxol in vivo. Serum PSA of mice, weightsof mice and PSA expression in xenograft tumors of mice by immunohistochemical methods were measured. Results Theconcentration of docetaxol above 10-7mol/L enhanced the growth suppression (suppression ratio≥47.5%, P<0.05), apoptosis(apoptosis ratio≥16.8%, P<0.01) and down-regulation of the expression of cyclin D1 (expression ratio≤10.8%, P<0.05),compared with the control 25.5%. Serum PSA of mice (9513)ng/ml P<0.01, weight of xenograft tumors (3.70.4)g, P<0.01and PSA expression in tumors (66.03.8)%, P<0.05 with PC-3prostate cancer cell lines of nude mice were all decreasedsignificantly in docetaxol group than in control except weights of mice (22.62.5)g, P<0.05. Conclusion Docetaxol canenhance the growth suppression and induce apoptosis of PC-3 cells in vitro and in vivo. It shows great potential in thetreatment of androgen-independent carcinoma of prostate.