Received:11 January 2019,
Published:15 August 2019
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Lin WAN, Yong CHENG, Wuyi WANG, et al. Advanced glycation end products enhance invasion and migration of colon cancer HCT116 cells in hypoxic microenvironment[J]. Journal of Third Military Medical University, 2019, 41(15): 1453-1460.
Lin WAN, Yong CHENG, Wuyi WANG, et al. Advanced glycation end products enhance invasion and migration of colon cancer HCT116 cells in hypoxic microenvironment[J]. Journal of Third Military Medical University, 2019, 41(15): 1453-1460. DOI: 10.16016/j.1000-5404.201901095.
Objective
2
To investigate the effects of advanced glycation end products (AGEs) on the proliferation
invasion
migration and epithelial-mesenchymal transition (EMT) of colon cancer HCT116 cells in hypoxic microenvironment.
Methods
2
The optimal AGEs concentration (200 μg/mL) and treatment time (48 h) fo
r promoting the proliferation of HCT116 cells were determined through a screening test with CCK-8 assay and used in subsequent experiment. HCT116 cells were treated with AGEs
hypoxia
or their combination
and the cell cycle changes were detected using flow cytometry; the changes in the invasive and migration abilities of the cells
in vitro
were assessed using Transwell chamber invasion and migration assays. The expressions of HIF-1α
RAGE
E-cadherin
N-cadherin
vimentin and MMP2 proteins in the treated cells were determined with Western blotting.
Results
2
Compared with the blank control cells
HCT116 cells exposed to a hypoxic microenvironment showed an increased proliferative activity
but AGEs alone did not significantly affect the cell proliferation. The cells treated with AGEs
hypoxia
and their combination all exhibited enhanced invasion and migration abilities compared with the blank control cells. The results of Western blotting showed that the expression level of HIF-1α
which was low in HCT116 cells in normoxic condition
was increased significantly in a hypoxic condition
and increased further after exposure of the cells to both AGEs and hypoxia. The expression of RAGE was increased after AGEs exposure of the cells in both normal and hypoxic environments
and the increase was more prominent in a hypoxic condition. Exposure to AGEs
hypoxia
and both all resulted in increased expressions of MMP2
N-cadherin and vimentin but lowered expression of E-cadherin in the cells.
Conclusion
2
AGEs can further enhance the invasive and migration abilities but has little effect on the proliferation of HCT116 cells exposed to a hypoxic environment.
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