Hu Wei, Gao Zhen-Yu, Wang Wei
Zhonghua Nan Ke Xue. 2014 Mar;20(3):218-24.
To investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines.
We treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively.
The proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P <0.05). At 24 hours, the apoptosis rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (14.41 +/- 1.32)% , (16.13 +/- 1.55)% and (14.48 +/- 1.42)% , and those of the LNCaP cells treated with 20 and 25 nmol/L bortezomib were (12.77 +/- 1.28)% and (14. 84 +/- 1.65)% , significantly higher than those of the control group (P <0.05) , and the DU145 cells showed an even higher sensitivity to bortezomib than the LNCaP cells. Bortezomib failed to sensitize these two cell lines to NK cell-mediated cytotoxicity in short-term assay, while long-term assay manifested that the apoptosis rates of DU145 and LNCaP cells after treated with 20 nmol/L bortezomib + NK cells were (41.83 +/- 5.06)% and (30.31 +/- 3.62)% , respectively, significantly higher
Bortezomib enhances the sensitivity of than those after treated with either bortezomib or NK cells alone (P <0.05). PCa cells to NK cell-mediated cytotoxicity and adds to the effect of current cancer therapies, and it is more efficacious for androgen-independent prostate cancer.
探讨硼替佐米能否增强人前列腺癌细胞（PCa）对自然杀伤（NK）细胞介导的细胞毒性的敏感性，以及其对不同PCa细胞系是否产生相同作用。
我们用浓度为0、5、10、15、20和25 nmol/L的硼替佐米处理雄激素依赖的PCa LNCaP细胞和雄激素非依赖的PCa DU145细胞24、48和72小时，然后分别通过CCK-8和Annexin V/PI检测肿瘤细胞的增殖和凋亡情况。
用15、20和25 nmol/L硼替佐米处理的DU145细胞在48小时时的增殖率分别为（82.79±2.04）%、（73.59±2.95）%和（74.16±6.16）%，在72小时时分别为（71.24±5.30）%、（51.20±2.91）%和（38.02±2.67）%；用15、20和25 nmol/L硼替佐米处理的LNCaP细胞在48小时时的增殖率分别为（77.04±7.74）%、（42.61±6.62）%和（23.85±6.04）%，在72小时时分别为（36.45±7.02）%、（14.94±5.76）%和（11.65±5.87）%，与对照组相比均显著受到抑制（P<0.05）。在24小时时，用15、20和25 nmol/L硼替佐米处理的DU145细胞的凋亡率分别为（14.41±1.32）%、（16.13±1.55）%和（14.48±1.42）%，用20和25 nmol/L硼替佐米处理的LNCaP细胞的凋亡率分别为（12.77±1.28）%和（14.84±1.65）%，显著高于对照组（P<0.05），且DU145细胞对硼替佐米的敏感性高于LNCaP细胞。在短期试验中，硼替佐米未能使这两种细胞系对NK细胞介导的细胞毒性敏感，而长期试验表明，用20 nmol/L硼替佐米+NK细胞处理后，DU145和LNCaP细胞的凋亡率分别为（41.83±5.06）%和（30.31±3.62）%，分别显著高于单独用硼替佐米或NK细胞处理后的凋亡率（P<0.05）。
硼替佐米增强了PCa细胞对NK细胞介导的细胞毒性的敏感性，并增强了当前癌症治疗的效果，且对雄激素非依赖型前列腺癌更有效。
