实用医学杂志 ›› 2021, Vol. 37 ›› Issue (2): 188-194.doi: 10.3969/j.issn.1006⁃5725.2021.02.012

• 基础研究 • 上一篇    下一篇

褪黑素通过调控EZH2表达增强食管癌细胞对5⁃氟尿嘧啶的敏感性

秦文兵,张月丽,刘嘉,李瑞佳,张锐
  

  1. 1 西安市第八医院药剂科(西安 710000);2 郑州市中心医院临床药学科(郑州 450007);3 陕西省肿瘤医院 重症医学科(西安 710000)

  • 出版日期:2021-01-25 发布日期:2021-01-25
  • 通讯作者: 张锐 E⁃mail:hndxzhangrui@163.com
  • 基金资助:
    河南省医学科技攻关计划项目(编号:2018020765)

Melatonin enhances the sensitivity of esophageal cancer cellsto 5⁃fluorouracil by regulating EZH2 expres⁃ sion

QIN Wenbing*,ZHANG Yueli,LIU Jia,LI Ruijia,ZHANG Rui
  

  1. Department of Pharmacy,the Eight Hos⁃pital of Xi′an,Xi′an 710000,China
  • Online:2021-01-25 Published:2021-01-25
  • Contact: ZHANG Rui E⁃mail:hndxzhangrui@163.com

摘要:

目的 探讨褪黑素(melatonin,MLT)协同 5⁃氟尿嘧啶(5⁃fluorouracil,5⁃FU)抑制食管癌细胞 的作用及其分子机制。方法 采用不同浓度的褪黑素和 5⁃FU 处理人食管癌 EC⁃9706 EC⁃109 细胞;通过 检测细胞活性、侵袭迁移、细胞凋亡和蛋白表达来探讨褪黑素对 5⁃FU 化疗敏感性的影响,进一步探索其 可能的作用机制。通过荷瘤实验探讨褪黑素和 5⁃FU 协同抗肿瘤的作用。结果 褪黑素对 EC⁃9706 EC⁃109 细胞活力的抑制呈剂量依赖性;与空白对照组相比,褪黑素能够降低 EC⁃9706 EC⁃109 细胞的侵 袭和迁移能力(P < 0.01),增加细胞的凋亡率(P < 0.01)。与单独褪黑素和 5⁃FU 药物处理组比较,褪黑素 5⁃FU 联合组显著降低食管癌细胞的增殖、侵袭和迁移,增加细胞凋亡(P < 0.01)。同时,与单独褪黑素 5⁃FU 药物处理组比较,褪黑素和 5⁃FU 联合组显著降低 EZH2 的表达。过表达 EZH2 能够逆转褪黑素 5⁃FU EC⁃9706 细胞的影响(P < 0.01)。此外,与单独 5⁃FU 给药组比较,褪黑素和 5⁃FU 联合给药显著 抑制裸鼠体内肿瘤的生长(P < 0.01)。结论 褪黑素和 5⁃FU 协同抑制 EZH2 的表达、促进食管癌细胞凋 亡,提高5⁃FU 

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Abstract:

Objective To investigate the inhibitory effect of melatonin in conjunction with 5⁃fluorouracil and its molecular mechanism in esophageal cancer. Methods Human esophageal carcinoma EC⁃9706 and EC⁃109 cells were treated with MLT and 5⁃FU at different concentrations.The effects of MLT on the chemotherapy sensitivi⁃ ty of 5⁃FU were investigated by detecting cell activity,invasion,migration,apoptosis and protein expression,and the possible mechanism was further explored.The synergistic antitumor effect of MLT and 5⁃FU was investigated by tumor⁃bearing experiment. Results MLT inhibited the activity of EC⁃9706 and EC⁃109 cells in a dose⁃dependent manner. Compared with blank controls,melatonin reduced the invasion and migration of EC ⁃ 9706 and EC ⁃ 109 cells(P < 0.01),but increased the apoptosis rate(P < 0.01). Compared with MLT and5⁃FU alone group,the combinational use of melatonin and 5⁃FU significantly reduced the proliferation,invasion,migration and apoptosis of esophageal carcinoma cells(P < 0.01). Meanwhile,compared with MLT and5⁃FU alone,the combinational use of melatonin and 5⁃FU significantly reduced EZH2 expression,and overexpression of EZH2 reversed the effects of MLT and 5⁃FU on EC⁃9706 cells(P < 0.01). In addition,MLT and 5⁃FU combined administration significantly inhibited the growth of esophageal cancer in nude mice compared with 5⁃FU alone(P < 0.01). Conclusion The combinational use of melatonin and 5⁃FU promotes apoptosis by inhibiting the expression of EZH2,thus improving 

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