Effects of Substrate Stiffness on Epithelial-Mesenchymal Transition of Colon Cancer Cells under Simulated Hypoxia Environment
10.16156/j.1004-7220.2023.02.09
- VernacularTitle:模拟低氧微环境中基质硬度对结肠癌细胞上皮-间质转化的影响
- Author:
Jing ZHANG
1
,
2
;
Jiajian ZHOU
3
;
Qingya DANG
4
;
Xinxin XU
4
;
Yinghao LIN
4
;
Xunxiao LI
4
;
Haibin LI
4
Author Information
1. Library of Jining Medical University, Jining 272067, Shandong, China
2. Institute of Precision Medicine, Jining Medical University
3. School of Clinical Medicine, Weifang Medical University
4. Institute of Precision Medicine, Jining Medical University
- Publication Type:Journal Article
- Keywords:
colon cancer cell;
substrate stiffness;
hypoxia;
epithelial-mesenchymal transition
- From:
Journal of Medical Biomechanics
2023;38(2):E261-E267
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects from the synergy of substrate stiffness and hypoxia on epithelial mesenchymal transition (EMT) of colon cancer cells SW480 by simulating the microenvironment of human colon cancer tissues. Methods Polyvinyl alcohol gels with different stiffness ( 4. 5, 20, 40 kPa) were prepared to simulate the stiffness of each part of colon cancer tissues. The morphological change of cells on substrate with different stiffness was detected under simulated hypoxia ( CoCl2 ) environment. The expression of hypoxia inducible factor (HIF-1α), and EMT markers E-cadherin, Vimentin, Snail 1 were detected by Western blot. The mRNA expression of E-cadherin, Vimentin, Snail 1, matrix metalloproteinase-2 ( MMP-2), and MMP-9 was detected by quantitative real-time PCR ( qRT-PCR). Results Under simulated hypoxia environment, with the increase of substrate stiffness, the SW480 cells spreading area increased, and transformed from round shape into irregular polygon. The EMT of SW480 could be enhanced through up-regulating expression of Vimentin, Snail 1, MMP-2, MMP-9, and down-regulating expression of E-cadherin. Conclusions This study is important for exploring the synergistic effect of substrate stiffness and hypoxia on the EMT of colon cancer cells as well as the molecular mechanism.