FoxM1对人宫颈癌顺铂耐药株Hela/DDP增殖、侵袭、凋亡的影响及其机制研究

Effect of FoxM1 on proliferation, invasion, and apoptosis of cisplatin resistant human cervical cancer cell line Hela/DDP and its mechanism

  • 摘要: 目的:探讨叉头框转录因子M1(FoxM1)对人宫颈癌顺铂耐药株Hela/DDP 增殖、侵袭、凋亡的影响及其机制。方法:将Hela/DDP细胞分为空白组(常规培养,不予任何处理)、正常对照(NC)组(转染空白干扰质粒)、低表达组和过表达组。低表达组转染siRNA-FoxM1 下调Hela/DDP 细胞中FoxM1 表达,过表达组转染pcDNA3.1-FoxM1 上调Hela/DDP 细胞中FoxM1 表达。采用RT-qPCR 法检测FoxM1 mRNA 表达水平,CCK-8 检测细胞活力,流式细胞仪检测细胞凋亡,Transwell小室检测细胞侵袭能力。结果:FoxM1 mRNA 在Hela 细胞中的表达水平低于Hela/DDP 细胞(P<0.05)。空白组与NC 组中FoxM1 mRNA、增殖率、凋亡率、侵袭细胞数及HSP70、S100A9蛋白表达水平比较,差异均无统计学意义(P>0.05)。与空白组比较,低表达组细胞活力和侵袭能力及FoxM1 mRNA、HSP70蛋白表达水平降低,凋亡率和S100A9蛋白表达水平升高(P<0.05),与空白组比较,过表达组细胞活力和侵袭能力及FoxM1 mRNA、HSP70 蛋白表达水平升高,凋亡率和S100A9 蛋白表达水平降低(P<0.05)。与低表达组比较,过表达组细胞活力和侵袭能力及FoxM1 mRNA、HSP70蛋白表达水平升高,凋亡率和S100A9蛋白表达水平降低(P<0.05)。结论:下调FoxM1表达可抑制HSP70表达,促进S100A9表达,调控宫颈癌细胞恶性行为,从而提高宫颈癌顺铂耐药细胞株对顺铂化疗的敏感性。

     

    Abstract: Objective: To investigate the effect of forkhead box M1 (FoxM1) on proliferation, invasion, and apoptosis of cisplatin resistant human cervical cancer strain Hela/DDP and its mechanism.Methods: Hela/DDP cells were divided into blank group (conventional culture without any treatment), normal control (NC) group (transfection with blank plasmid), low-expression group, and overexpression group.The low-expression group transfected with siRNA-FoxM1 to downregulate the expression of FoxM1 in Hela/DDP cells, while the overexpression group cells transfected with pcDNA3.1-FoxM1 to upregulate the expression of FoxM1 in Hela/DDP cells.The expression level of FoxM1 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR).The cell viability was detected by CCK-8.Apoptosis was detected by flow cytometry, and invasive ability of cells was detected by Transwell.Results: The expression level of FoxM1 mRNA in Hela cells was lower than that in Hela/DDP cells (P< 0.05).There was no significant difference in FoxM1 mRNA, proliferation rate, apoptosis rate, the number of invasive cells, and the expression levels of HSP70 and S100A9 proteins between the blank group and the NC group (P> 0.05).Compared with the blank group, the cell viability and invasive ability as well as the expression levels of FoxM1 mRNA and HSP70 protein in the low-expression group decreased, while the apoptosis rate and S100A9 protein expression level increased (P< 0.05).Compared with the blank group, the cell viability and invasive ability as well as the expression levels of FoxM1 mRNA and HSP70 protein in the overexpression group increased, while the apoptosis rate and S100A9 protein expression level decreased (P< 0.05).Compared with the low-expression group, the cell viability, invasion ability, and expression levels of FoxM1 mRNA and HSP70 protein elevated in the overexpression group, while the apoptosis rate and S100A9 protein expression level reduced (P< 0.05).Conclusion: Down-regulating the mRNA level of FoxM1 can inhibit the expression of HSP70, promote the expression of S100A9, and regulate the malignant behavior of cervical cancer cells, thereby improving the sensitivity of cervical cancer cell lines resistant to cisplatin chemotherapy.

     

/

返回文章
返回