蛋白激酶Cζ抑制剂对人乳腺癌细胞侵袭迁移力的影响

Effect of protein kinase Cζinhibitor on invasion and metastasis of human breast cancer cell MDA-MB-231

目的探讨蛋白激酶C(PKC)ζ抑制剂T1038-2546对人乳腺癌细胞侵袭迁移力的影响。方法体外应用美国经典Z'-LYTETM试剂盒筛选出PKCζ的高效抑制剂T1038-2546,其半数抑制浓度(IC50)约为30μmol/L;通过观察T1038-2546处理人乳腺癌MDA-MB-231细胞前后细胞的生长速度,细胞周期分布以及细胞侵袭迁移能力的改变,探讨T1038-2546对乳腺癌细胞MDA-MB-231恶性生物学行为的影响。结果与DMSO处理的MDA-MB-231细胞(对照组)相比,低浓度T1038-2546处理的细胞(实验组)生长速度没有明显改变,而90和180μmol/L T1038-2546处理的MDA-MB-231细胞生长速度明显减慢(P<0.05),并且呈现时间依赖性;实验组与对照组细胞相比,细胞周期分布差异无显著性(P>0.05);体外迁移实验结果显示,与对照组细胞相比,30μmol/L T1038-2546处理组细胞的迁移能力明显减弱(P<0.05);体外侵袭实验结果显示,30μmol/L T1038-2546处理组细胞的穿膜细胞数明显少于对照组细胞的穿膜细胞数,差异有显著性(P<0.05)。结论蛋白激酶Cζ抑制剂T1038-2546可显著抑制人乳腺癌细胞MDA-MB-231的侵袭迁移力。

Objective To investigate the effect of protein kinase C（PKC）ζinhibitor T1038-2546 on invasion and metastasis of human breast cancer cell MDA-MB-231.Methods Through Z＇-LYTETM kit screen an effective PKC ζ inhibitor T1038-2546 with an IC50 value at 30μmol/L.The effects of T1038-2546 on the malignant characters of MDA-MB-231 cells including cellular proliferation rate,the activities of invasion and metastasis were studied by observing changes of the growth rate,distribution of cell cycle and invasion and migration abilities of MDA-MB-231 cells before and after T1038-2546 treatment.Results Compared with those of the DMSO treated MDA-MB-231 cells（control group）,the growth rate was suppressed markedly（P0.05） in the MDA-MB-231 cells treated with 90 or 180μmol/L T1038-2546（experimental group） and the changes presented time-dependence patterns,while no changes were found in the MDA-MB-231 cells treated with low concentrations of T1038-2546.Furthermore,there was no significant difference（P0.05） for the distribution of cell cycle in the control group and experimental group.Moreover,the results from migration assay in vitro indicated that compared with that of the control group cells,the migration abilities of MDA-MB-231 cells treated with 30μmol/L T1038-2546 were decreased dramatically（P0.05）.Invasion assay results showed that compared with that of the control group cells,cell number on the down-side of transwell membrane was significantly lower in the MDA-MB-231 cells treated with 30μmol/L T1038-2546,with a significant difference（P0.05）.Conclusion PKC ζ inhibitor T1038-2546 could significantly inhibit the abilities of invasion and metastasis of human breast cancer cells MDA-MB-231 in vitro.