张月, 张斌, 冯炜红, 李媛媛, 曹旭晨. ZM447439对乳腺癌T47D细胞生长和细胞周期的影响[J]. 中国肿瘤临床, 2011, 38(22): 1383-1386. DOI: 10.3969/j.issn.1000-8179.2011.22.007
引用本文: 张月, 张斌, 冯炜红, 李媛媛, 曹旭晨. ZM447439对乳腺癌T47D细胞生长和细胞周期的影响[J]. 中国肿瘤临床, 2011, 38(22): 1383-1386. DOI: 10.3969/j.issn.1000-8179.2011.22.007
Yue ZHANG, Bin ZHANG, Weihong FENG, Yuanyuan LI, Xuchen CAO. Effects of Aurora Kinase Inhibitor ZM447439 on Cell Growth and Cycle of Breast Cancer Cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2011, 38(22): 1383-1386. DOI: 10.3969/j.issn.1000-8179.2011.22.007
Citation: Yue ZHANG, Bin ZHANG, Weihong FENG, Yuanyuan LI, Xuchen CAO. Effects of Aurora Kinase Inhibitor ZM447439 on Cell Growth and Cycle of Breast Cancer Cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2011, 38(22): 1383-1386. DOI: 10.3969/j.issn.1000-8179.2011.22.007

ZM447439对乳腺癌T47D细胞生长和细胞周期的影响

Effects of Aurora Kinase Inhibitor ZM447439 on Cell Growth and Cycle of Breast Cancer Cells

  • 摘要: 研究Aurora激酶抑制剂ZM447439对体外培养的人乳腺癌细胞T47D生长和细胞周期各时相的影响。方法:采用四甲基偶氮唑盐法测定ZM447439对乳腺癌T47D细胞增殖的影响;克隆形成实验检测ZM447439对T47D细胞增殖的影响;流式细胞术检测ZM447439对乳腺癌T47D细胞周期各时相的影响。Western blot检测ZM447439对Aurora A,p-AuroraA,Histone H3,p-Histone H3以及CyclinB1的影响。结果:不同浓度的ZM447439处理T47D细胞24、48、72h明显抑制T47D细胞增殖,IC50分别为(9.604±0.982)μmol/L、(3.413±0.533)μmol/L、(0.620±0.208)μmol/L;经药物作用24h后,贴壁细胞出现皱缩、变圆、脱落;克隆形成率由(93.00±2.65)%降至0%;流式细胞术显示G0/G1期细胞由(50.50±1.71)%降至(6.30±0.17)%,S期细胞由(32.50±2.70)%降至0%,G2/M期细胞由(17.00±4.39)%升高至(93.70±0.17)%,G2/M期的阻滞呈现剂量依赖性;Western blot显示Aurora A、Histone H3无明显趋势变化,p-AuroraA、p-Histone H3、CyclinB1随着浓度的增加而减少,都呈现一定的剂量依赖性。结论:ZM447439可抑制T47D细胞生长,产生G2/M期阻滞。

     

    Abstract: To investigate the effects of ZM447439, a new Aurora kinase inhibitor, on the growth and cell cycle of T47D breast cancer cell lines in vitro. Methods: T47D was cultured in a medium for 24 h that contained different concentrations of ZM447439. Cell morphological changes were observed under an inverted microscope. The effects of ZM447439 on cell proliferation were examined via the mono-nuclear cell direct cytotoxicity assay and colony assay. The cell cycle of T47D cells was determined using flow cytometry. The levels of phosphorated AuroraA ( p-AuroraA ), total Aurora A ( T-Aurora A ), phosphorated Histone H3 ( p-Histone H3 ), total Histone H3 ( T-Histone H3 ), and CyclinB1 were determined using Western blot. Results: ZM447439 obviously inhibited the proliferation of T47D cells after 24, 48, or 72 h treatment in a dose- and time-dependent manner, with IC50 values of ( 9.604 ± 0.982 ) μmol/L, ( 3.413 ± 0.533 ) μmol/L, and (0.620±0.208) μmol/L, respectively. After treatment with ZM447439, apoptosis of the T47D cells occurred. Clonogenic assay was performed to elucidate the possible differences in the long-term effects of ZM447439 on human breast cells. The ratio of colony-forming was decreased from ( 93.00 ± 2.65 ) % to 0, the ratio of G0/G1 phase was decreased from ( 50.50 ± 1.71 ) % to ( 6.30 ± 0.17 ) %, that of S was decreased from ( 32.50 ± 2.70 ) % to 0, and the percentage of G2/M cells was increased from ( 17.00 ± 4.39 ) % to ( 93.70±0.17 ) %  ( P < 0.05 ). Flow cytometry showed the G2/M arrest in a dose-dependent manner. ZM447439 inhibited p-AuroraA, p-Histone H3, and Cyclin B1. ZM447439 had no significant effect on the expression of T-Aurora A and T-Histone H3. Conclusion: ZM447439 may inhibit the growth of T47D cells and induce their G2/M arrest, indicating its potential as a new approach in treating breast cancer.

     

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