| 马玉花,张泽高,马苗苗,等.极光激酶 A抑制剂 MLN8237对宫颈鳞状细胞癌细胞顺铂化疗敏感性的影响[J].安徽医药,2020,24(5):865-868. |
| 极光激酶 A抑制剂 MLN8237对宫颈鳞状细胞癌细胞顺铂化疗敏感性的影响 |
| Effect of aurora A inhibitor MLN8237 on chemosensitivity of cervical squamous cell carcinoma cells to cisplatin |
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| DOI：10.3969/j.issn.1009?6469.2020.05.004 |
| 中文关键词: 宫颈肿瘤 蛋白质丝氨酸苏氨酸激酶 极光激酶 A MLN8237 顺铂 细胞增殖 细胞凋亡 体外研究 |
| 英文关键词: Uterine cervical neoplasms Protein?serine?threonine kinases Aurora A MLN8237 Cisplatin Cell proliferation Apoptosis In vitro |
| 基金项目:新疆维吾尔自治区自然科学青年基金项目( 2017Do1C149) |
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| 中文摘要: |
| 目的探讨极光激酶 A(Aurora?A，Aurora A)抑制剂 MLN8237对人宫颈鳞状细胞癌细胞(HCC94)顺铂( cisplatin)化疗敏感性的影响。方法采用不同浓度 MLN8237联合顺铂在不同时间作用于 HCC94细胞，用四唑盐( MTT)比色法观察药物对细胞生长的抑制，蛋白质印迹法( Western Blotting)分析胞质内 P21wap1、P53、P(S315)?P53、Aurora A和 P(288)?Aurora A蛋白的表达；用流式细胞术检测细胞凋亡。结果 MLN8237(10~160 μmol/L)或顺铂( 10~160 μmol/L)均明显抑制 HCC94细胞的生长( P＜ 0.05)并引起细胞凋亡；小剂量 MLN8237(5、10和 20 μmol/L)和顺铂( 2.5、5、10和 20 μmol/L)联合应用，与单用顺铂比较，可明显增加细，胞增殖抑制率和细胞凋亡率(均 P＜0.05)。与对照组比较， MLN8237处理组 P21wap1和 P53表达显著增高， P(S315)? P53和 P(T288)?Aurora A表达显著降低， Aurora A表达不改变。与对照组比较，顺铂组 P21wap1/Cip1和 P53表达轻微增高， P(S315)?P53表达轻微降低， Aurora A和 P(T288)?Aurora A蛋白表达不改变。与各单药组和对照组比较，联合组对以上各种蛋白的影响作用显著加强。结论小剂量 MLN8237可增强宫颈鳞状细胞癌细胞 HCC94对顺铂的敏感性，增强化疗疗效。 |
| 英文摘要: |
| Objective To investigate the effect of MLN8237，an inhibitior of Aurora?A(Aurora A)，on the sensitivity of human cer?vical squamous cell carcinoma line HCC94 to cisplatin chemotherapy and its possible mechanisms.Methods Different concentra?tions of MLN8237 combined with cisplatin were used to treat HCC94 cells at different times.MTT assay was used to observe the in?hibitory effect on cell growth.The expression of P21wap1，P53，P(S315)?P53，Aurora A and P(T288)?Aurora A protein expression in the cytoplasm were analyzed by Western Blotting.Flow cytometry was used to detect apoptosis.Results Both MLN8237(10~160 μmol/L)and cisplatin(10~160 μmol/L)significantly inhibited the growth of HCC94 cells(P＜0.05)，and induced apoptosis. Combination of low dose MLN8237(5，10 and 20 mol/L)and cisplatin(2.5，5，10 and 20 mol/L)resulted in more significant inhibi?tion on growth and apoptosis of HCC94 cells than cisplatin alone(all P＜0.05).Compared with the control group，the MLN8237 treatment group showed significantly higher expression of P21wap1 and P53，significantly lower expression of P(S315)?P53 and P(T288)?Aurora A，and no change inAurora A.Compared with the control group，P21wap1/Cip1 and P53 was decreased，and P(S315)?P53 expression was decreased.The expression of Aurora A，P(T288)?Aurora A protein was not changed in the cisplatin group.Compared with the single drug group and the control group，the effect of the combination group on the above proteins was sig? nificantly enhanced.Conclusion Low dose of MLN8237 can enhance the sensitivity of cervical squamous cell carcinoma cells to cisplatin，thus enhancing the curative effect and provide reference for further research. |
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