美登木素对人甲状腺癌细胞增殖、侵袭、迁移、凋亡和自噬的影响

doi:10.11904/j.issn.1002-3070.2025.01.004

实用肿瘤学杂志 ›› 2025, Vol. 39 ›› Issue (1): 21-29.doi: 10.11904/j.issn.1002-3070.2025.01.004

美登木素对人甲状腺癌细胞增殖、侵袭、迁移、凋亡和自噬的影响

顾娜¹, 谭珵¹, 王璐瑶¹, 沈洪昇¹, 李锡晶¹, 李新燕², 刘翠翠², 赵秀梅¹

1.天津市医药科学研究所肿瘤药物研究室(天津 300020);
2.沧州医学高等专科学校药理教研室

收稿日期:2024-08-28 修回日期:2024-12-03 出版日期:2025-02-28 发布日期:2025-03-19
通讯作者: 刘翠翠,E-mail:65549465@qq.com
作者简介:顾娜,女,(1982-),硕士,助理研究员,从事中药药理及肿瘤药理相关的研究。
基金资助:
沧州市重点研发计划项目(编号:204106038);天津市第二批卫生健康行业高层次人才选拔培养工程(编号:TJSJMYXYC-D2-034)

Effects of maytansine on proliferation,migration,invasion,apoptosis and autophagy of human thyroid cancer cells

GU Na¹, TAN Cheng¹, WANG Luyao¹, SHEN Hongsheng¹, LI Xijing¹, LI Xinyan², LIU Cuicui², ZHAO Xiumei¹

1. Department of Oncology Medicine Laboratory,Tianjin Institute of Medical and Pharmaceutical Sciences,Tianjin 300020,China;
2. Department of Pharmacological teaching and research,Cangzhou Medical College

Received:2024-08-28 Revised:2024-12-03 Online:2025-02-28 Published:2025-03-19

摘要/Abstract

摘要： 目的探究美登木素对人甲状腺癌细胞C643增殖、侵袭、迁移、凋亡和自噬的影响。方法采用不同浓度(0.049、0.195、0.781、3.125、12.5、50、200 μmol/L)的美登木素溶液处理C643细胞,磺酰罗丹明B(sulforhodamine B,SRB)法检测美登木素对C643细胞增殖的影响,并确定后续实验加药浓度。取对数生长期的C643细胞,分为对照组、美登木素低剂量组、中剂量组及高剂量组,通过细胞划痕实验和Transwell小室实验检测美登木素对C643细胞侵袭和迁移能力的影响;2′,7′-二氢二氯荧光素二乙酸酯(2,7-dichlorodihydrofluorescein diacetate,DCFH-DA)荧光探针实验检测细胞内活性氧(reactive oxygen species,ROS)水平;流式细胞术检测细胞凋亡率,Western blot法检测细胞中凋亡及自噬相关蛋白的表达水平。结果 SRB法检测结果显示,浓度为0.049、0.195、0.781、3.125、12.5、50、200 μmol/L的美登木素溶液均能抑制C643细胞增殖(P＜0.05),且呈明显的浓度-时间依赖性,24、48和72 h的半数抑制浓度(half maximal inhibitory concentration,IC₅₀)分别为54.255、5.193和0.647 μmol/L;细胞划痕实验和Transwell小室实验结果显示,浓度为0.1、1、10 μmol/L的美登木素溶液能浓度依赖性地降低C643细胞的迁移(P＜0.05)和侵袭能力(P＜0.01);荧光探针实验结果显示,浓度为0.1、1、10 μmol/L的美登木素溶液能浓度依赖性地升高C643细胞内ROS水平(P＜0.01);流式细胞术结果显示,浓度为0.1、1、10 μmol/L的美登木素溶液能浓度依赖性地升高C643细胞凋亡率(P＜0.01);Western blot实验结果显示随着美登木素浓度的增加,C643细胞内凋亡相关蛋白Bax表达水平升高(P＜0.05),Bcl-2表达水平降低(P＜0.05),同时自噬相关蛋白LC3Ⅱ/Ⅰ(P＜0.05)和Beclin-1(P＜0.01)的表达水平升高,p62表达水平降低(P＜0.001)。结论美登木素可以抑制人甲状腺癌C643细胞增殖、侵袭和迁移,并可通过升高细胞内ROS水平诱导细胞凋亡和自噬协同作用。

关键词: 美登木素, 人甲状腺癌细胞, 细胞凋亡, 自噬

Abstract: Objective The Objective of this study was to investigate the effects of maytansine on proliferation,migration,invasion,apoptosis and autophagy of human thyroid cancer C643 cells. Methods C643 cells were treated with different concentrations(0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L)of maytansine,the effect of maytansine on the proliferation of C643 cells was detected by the sulforhodamine B(SRB)method,and the concentration of subsequent experiments was determined.C643 cells in the logarithmic growth stage period were divided into the control group,low-dose group,mid-dose group and high-dose group.The effects of maytansine on migration and invasion abilities of C643 cells were detected by cell scratch and Transwell chamber assay;The levels of reactive oxygen species(ROS)were detected by 2 ′,7 ′-dichlorofluorescein diacetate(DCFH-DA)fluorescent probe experiment;The apoptosis rate of C643 cells was detected by flow cytometry;The expression of proteins related to apoptosis or autophagy was detected by Western blot. Results Maytansine at concentrations of 0.049,0.195,0.781,3.125,12.5,50 and 200 μmol/L could inhibit the proliferation of C643 cells(P＜0.05),and exhibited a significant concentration time dependence.The half maximal inhibitory concentrations(IC₅₀)at 24,48 and 72 h were 54.255,5.193 and 0.647 μmol/L,respectively;The cell scratch and Transwell chamber results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could reduce the migration and invasion abilities of C643 cells(P＜0.05 and P＜ 0.01).The fluorescence probe results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could increase the intracellular ROS levels of C643 cells(P＜0.01).The flow cytometry results showed that maytansine at concentrations of 0.1,1 and 10 μmol/L could concentration dependently increase the apoptosis rate of C643 cells(P＜0.01).The Western blot results showed that with the increase of maytansine concentrations,the expression of Bax protein related to apoptosis in C643 cells increased(P＜0.05),the expression of Bcl-2 decreased(P＜0.05),the expression of LC3II/I(P＜0.05)and Beclin-1(P＜0.01)increased,while the expression of p62 decreased(P＜0.001). Conclusion Maytansine can inhibit the proliferation,migration and invasion of human thyroid cancer C643 cells,and induce the synergistic effect on apoptosis and autophagy by increasing intracellular ROS levels.

Key words: Maytansine, Human thyroid cancer cells, Cell apoptosis, Autophagy

中图分类号:

R736.1

顾娜, 谭珵, 王璐瑶, 沈洪昇, 李锡晶, 李新燕, 刘翠翠, 赵秀梅. 美登木素对人甲状腺癌细胞增殖、侵袭、迁移、凋亡和自噬的影响[J]. 实用肿瘤学杂志, 2025, 39(1): 21-29.

GU Na, TAN Cheng, WANG Luyao, SHEN Hongsheng, LI Xijing, LI Xinyan, LIU Cuicui, ZHAO Xiumei. Effects of maytansine on proliferation,migration,invasion,apoptosis and autophagy of human thyroid cancer cells[J]. Journal of Practical Oncology, 2025, 39(1): 21-29.

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美登木素对人甲状腺癌细胞增殖、侵袭、迁移、凋亡和自噬的影响

Effects of maytansine on proliferation,migration,invasion,apoptosis and autophagy of human thyroid cancer cells

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