摘要
目的探讨多聚腺苷二磷酸核糖聚合酶(poly ADP-ribosepolymerase,PARP)抑制剂AG014699辅助多西他赛或卡铂对三阴性乳腺癌(triple negative breast cancer,TNBC)细胞株MDA-MB-231增殖的干预能力.方法实验购置使用细胞增殖与细胞毒性检测试剂盒(CCK-8)检测各阶段浓度(0.1、1.0、10.0、20.0和40.0μmol/L)的PARP抑制剂AG014699、多西他赛(10-9、10-8、10-7、10-6、10-5 mol/L)和卡铂(10-6、10-5、10-4、10-3 mol/L)对MDA-MB-231细胞增殖的影响,采用组织学流式细胞学检测技术检测细胞周期分布情况和凋亡.结果 PARP 抑制剂 AG01469不同浓度(0.1、1.0、10.0、20.0、40.0 μmol/L)对 MDA-MB-231细胞增殖活性的干预能力分别为(94.83±3.93)%、(79.42±5.52)%、(63.75±4.34)%、(38.97±8.42)%、(29.70±3.35)%,各阶段比较差异有统计学意义(F=75.54、P<0.01,不同浓度间两两比较P均<0.05). PARP 抑制剂 AG014699联合不同浓度多西他赛对细胞增殖活性的干预能力[(69.77±17.94)%、(58.34±2.59)%、(52.81±2.01)%、(41.23±3.38)%、(24.82±0.73)%]与单药多西他赛[(81.24±11.91)%、(85.74±3.10)%、(72.74±4.66)%、(55.18±3.19)%、(45.95±3.82)%]的疗效比较,差异有统计学意义(t值分别为-0.923、-11.748、-6.802、-5.199、-9.410,其中10-9浓度时P>0.05,余各浓度P均<0.01). PARP 抑制剂 AG014699联合不同浓度卡铂[(78.33±2.89)%、(60.44±1.95)%、(50.55±3.07)%、(12.07±1.63)%]与卡铂单药(90.00±6.18)%、(87.87±2.30)%、(76.82±3.37)%、(40.71±1.68)%]进行疗效对比,细胞活性明显降低,差异有统计学意义(t值分别为-1.935、-15.756、-9.981、-21.192,其中10-6浓度时P>0.05,余各浓度P均<0.05). PARP 抑制剂 AG014699同10-3mol/L卡铂联合,q值>1.15,结果显示协同效应,与其他有效浓度的多西他赛或卡铂联合,q值均介于 0.85~1.15之间,显示相加效应.结论PARP 抑制剂AG014699辅助多西他赛或卡铂可以进一步抑制三阴性乳腺癌细胞株MDA-MB-231的增殖生长能力.通过单纯相加或者协同效应等药理机制,对三阴性乳腺癌细胞起到抑制作用.
Objective To investigate the effects of poly adenosine diphosphate ribose polymerase (PARP)inhibitor AG014699 on the proliferation of triple negative breast cancer (TNBC)cell line MDA-MB-231. Methods Cell proliferation and cytotoxicity test kit (CCK-8)was used to detect the proliferation of MDA-MB-231 cells in different concentrations of AG014699 (0.1, 1.0, 10.0, 20.0 and 40.0 mmol/L), DTX (10-9, 10-8, 10-7, 10-6 and 10-5 mol/L)and CBP (10-6, 10-5, 10-4 and 10-3 mol/L). Flow cytometry was used to detect cell apoptosis and cell cycle distribution. Results The effects of AG01469 at different concentrations (0.1, 1.0, 10.0, 20.0 and 40.0 μmol/L)on proliferation activity of MDA-MB-231 cells were(94.83±3.93)%,(79.42±5.52)%,(63.75±4.34)%,(38.97±8.42)%,(29.70±3.35)%, with statistically significant differences (F=75.54, P<0.01, different concentrations pairwise comparison: all P<0.05). The efficacy of AG014699 in combination with DTX at different concentrations ((69.77±17.94)%,(58.34±2.59)%,(52.81±2.01)%,(41.23±3.38)%,(24.82±0.73)%)was compared with that of single DTX ((81.24±11.91)%,(85.74±3.10)%,(72.74±4.66)%,(55.18±3.19)%,(45.95±3.82)%). The differences were statistically significant (t values were -0.923,-11.748,-6.802,-5.199,-9.410, respectively, with P>0.05 at 10-9 concentration and P<0.01 at all other concentrations). The efficacy of AG014699 combined with CBP ((78.33±2.89)%,(60.44±1.95)%,(50.55±3.07)%,(12.07±1.63)%)and single CBP ((90.00±6.18)%,(87.87±2.30)%,(76.82±3.37)%,(40.71±1.68)%)was compared, and the cell activity was significantly reduced, indicating statistically significant differences (t values were -1.935,-15.756,-9.981,-21.192, respectively, and P>0.05 at 10-6 concentration, P<0.05 at all the other concentrations). The q value was>1.15 when AG014699 was combined with 10-3 mmol/L CBP, which showed synergistic effect.When combined with other effective concentrations of DTX or CBP, the q value was between 0.85 and 1.15, showing additive effect. Conclusion PARP inhibitor AG014699 assisted DTX or CBP can inhibit the proliferation of TNBC cell line MDA-MB-231.By means of simple addition or systematic effect, it can inhibit the triple negative breast cancer.
作者
张晋冀
李忠辉
李长仔
孟丽军
张秀军
Zhang Jinji;Li Zhonghui;Li Changzai;Meng Lijun;Zhang Xiujun(Department of Oncology, Affiliated Hospital of North China University of Technology, Tangshan 063000, China;Department of Environmental and Chemical Engineering, Tangshan University, Tangshan 063000, China;Psychological college, North China University of Science and Technology, Tangshan 063000, China)
出处
《中国综合临床》
2019年第5期421-425,共5页
Clinical Medicine of China
基金
河北省自然科学基金资助项目(C2017209062).
关键词
三阴性乳腺癌
多聚腺苷二磷酸核糖聚合酶
多西他赛
卡铂
Triple negative breast cancer
Poly adenosine diphosphate ribose polymerase
Docetaxel
Carboplatin
作者简介
通信作者:张秀军,Email:rajiejinji@163.com.
