ICG-001对食管鳞癌细胞增殖的抑制作用及其分子机制

doi:10.3969/j.issn.1004-616x.2023.03.005

癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (3): 187-191,196.doi: 10.3969/j.issn.1004-616x.2023.03.005

• 论著 • 上一篇

ICG-001对食管鳞癌细胞增殖的抑制作用及其分子机制

史建红, 陈丁雄, 卢晓童, 郝佳洁, 蔡岩, 王明荣, 张钰

国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院, 分子肿瘤学国家重点实验室, 北京 100021

收稿日期:2023-03-09 修回日期:2023-04-21 发布日期:2023-06-03
通讯作者: 张钰
作者简介:史建红,E-mail:jianhong_SJH@163.com。
基金资助:
国家自然科学基金(81872279)

Inhibitory effect of ICG-001 on proliferation of esophageal squamous carcinoma cells and its molecular mechanisms

SHI Jianhong, CHEN Dingxiong, LU Xiaotong, HAO Jiajie, CAI Yan, WANG Mingrong, ZHANG Yu

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2023-03-09 Revised:2023-04-21 Published:2023-06-03

摘要/Abstract

摘要： 目的：检测小分子抑制剂ICG-001对食管鳞癌细胞增殖的抑制作用并探讨其分子机制。方法：使用50和100 μmol/L的小分子抑制剂ICG-001处理食管鳞癌细胞系KYSE410和KYSE450，以溶剂DMSO处理细胞作为对照，进行细胞增殖活力、集落形成能力、细胞周期分布及凋亡检测；分别使用实时荧光定量PCR(qPCR)和Western blot检测ICG-001处理细胞中相关分子(SKP2、Survivin和TCF4)mRNA和蛋白水平的表达变化。结果：与对照组比较，ICG-001处理可显著抑制食管鳞癌细胞系KYSE410和KYSE450的增殖活力和集落形成能力，并可显著诱导细胞发生G0/G1期阻滞(P<0.01)；SKP2、Survivin和TCF4的mRNA和蛋白表达水平在ICG-001处理组均显著降低(P<0.01)。结论：ICG-001可显著抑制食管鳞癌细胞的增殖活力和集落形成能力，并可诱导细胞发生G0/G1期阻滞，该作用可能与其抑制β-catenin/TCF4的转录活性及其下游分子Survivin和SKP2的表达有关。

关键词: ICG-001, 食管鳞癌, 增殖能力, 细胞周期, 小分子抑制剂

Abstract: OBJECTIVE：To investigate effects of small molecule inhibitor ICG-001 on malignant phenotypes of esophageal squamous carcinoma (ESCC) cells and to explore its molecular mechanisms. METHODS：The ESCC cell lines KYSE410 and KYSE450 were treated with ICG-001 of 50 and 100 μmol/L，or with solvent DMSO as control. Treated cells were evaluated for cell proliferation viability，colony formation ability，cell cycle distribution and apoptosis. mRNA and protein expression of related molecules (SKP2，Survivin，and TCF4) were detected by real-time PCR (qPCR) and Western blot. RESULTS：Compared with the control group，ICG-001 treatment significantly inhibited the proliferation and colony formation ability of KYSE410 and KYSE450，and significantly induced G0/G1 phase arrest (P<0.01). In addition，expression levels of SKP2、Survivin and TCF4 were significantly decreased (P<0.01). CONCLUSION：ICG-001 significantly inhibited the proliferation viability and colony formation ability，and induced G0/G1 phase arrest of the two ESCC cell lines. The mechanisms may be related to the inhibition of b-catenin/TCF4 transcriptional activity and the expression of downstream molecules：Survivin and SKP2.

Key words: ICG-001, esophageal squamous cell carcinoma, proliferation, cell cycle, small molecule inhibitor

中图分类号:

R735.1

史建红, 陈丁雄, 卢晓童, 郝佳洁, 蔡岩, 王明荣, 张钰. ICG-001对食管鳞癌细胞增殖的抑制作用及其分子机制[J]. 癌变·畸变·突变, 2023, 35(3): 187-191,196.

SHI Jianhong, CHEN Dingxiong, LU Xiaotong, HAO Jiajie, CAI Yan, WANG Mingrong, ZHANG Yu. Inhibitory effect of ICG-001 on proliferation of esophageal squamous carcinoma cells and its molecular mechanisms[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(3): 187-191,196.

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ICG-001对食管鳞癌细胞增殖的抑制作用及其分子机制

Inhibitory effect of ICG-001 on proliferation of esophageal squamous carcinoma cells and its molecular mechanisms

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