硼替佐米增强前列腺癌细胞对自然杀伤细胞介导的细胞毒性的敏感性

[Bortezomib enhances the sensitivity of prostate cancer cells to natural killer cell-mediated cytotoxicity].

作者信息

Hu Wei, Gao Zhen-Yu, Wang Wei

出版信息

Zhonghua Nan Ke Xue. 2014 Mar;20(3):218-24.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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

CONCLUSION

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.

摘要

目的

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。

方法

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。

结果

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）。