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

作　　者：马玉花 张泽高[3] 马苗苗 热伊拉·麦买提伊敏[3] 开丽曼·阿不都巴热[3] 杨杰[3] 祁小丽[3] MA Yuhua;ZHANG Zegao;MA Miaomiao;REYILA·Maimaitiyimin;KAILIMAN·Abudubare;YANG Jie;QI Xiaoli(Department of Pathology,Karamay Central Hosptial of Xinjiang Karamay,Karamay,Xinjiang Uygur Autonomous Region 834000,China;Department of Pathology,Oriental Hospital Affiliated to Tongji University,Shanghai 200092,China;Radiotherapy Second Branch,The People’s Hospital of Xinjiang Uygur Autonomous Region,Urumchi,Xinjiang Uygur Autonomous Region 830001,China)

机构地区：[1]克拉玛依市中心医院病理科,新疆维吾尔自治区克拉玛依834000 [2]同济大学附属东方医院病理科,上海200092 [3]新疆维吾尔自治区人民医院放疗二科,新疆维吾尔自治区乌鲁木齐830001

出　　处：《安徽医药》2020年第5期865-868,I0001,共5页Anhui Medical and Pharmaceutical Journal

基　　金：新疆维吾尔自治区自然科学青年基金项目(2017Do1C149)。

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(10~160μmol/L)或顺铂(10~160μmol/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20μmol/L)和顺铂(2.5、5、10和20μmol/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。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(10~160μmol/L)and cisplatin(10~160μmol/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.

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 

分 类 号：R96[医药卫生—药理学]