Research articles
ScienceAsia 50 (2024):ID 2024038 1-10 |doi:
10.2306/scienceasia1513-1874.2024.038
Role and mechanism of FDFT1 in regulating ferroptosis in
colon cancer cells via the Nrf2/GPX4 pathway
Lin Moa, Xiaolin Wanga, Xin Liua, Jian Gaoa, Chao Tanb, Shunhai Jiana,*
ABSTRACT: This study was to investigate the role of FDFT1 in colon cancer SW480 cells and its potential molecular
mechanism. The survival prognosis of colon cancer patients was analyzed by TCGA database. FDFT1 mRNA expression
in FHC, SW480, HCT116, and HT29 was analyzed by RT-qPCR. FDFT1 was overexpressed using pcDNA-FDFT1. Cell
viability was measured by the CCK-8. Flow cytometry was used to detect cell death and ROS. Iron ion and LPO were
also measured. The ultrastructure of SW480 cells was detected by TEM. The cellular behavior of SW480 was detected
by wound healing and transwell invasion. GPX4 was detected by immunofluorescence. Western blot analysis was
performed to detect FDFT1, Nrf2, HO-1, and GPX4. The results showed that FDFT1 was a positive factor in the
prognosis of colon cancer. pcDNA-FDFT1 could lead to an increase in iron ion content and LPO in SW480. pcDNAFDFT1 and erastin inhibited the proliferation of SW480 and affected ROS and mitochondrial structure. The ferroptosis
inhibitor lip-1 inhibited the regulation of cell viability and ROS by pcDNA-FDFT1. pcDNA-FDFT1 and erastin inhibited
the expression of Nrf2, HO-1, and GPX4. The Nrf2 agonist oltipraz reversed the effects of pcDNA-FDFT1 and restored
the proliferation, migration, and invasive ability of SW480. The inhibition of Nrf2, HO-1, and GPX4 by pcDNA-FDFT1
was also up-regulated by oltipraz. In conclusion, up-regulation of FDFT1 induced iron death in SW480 cells through
the Nrf2/GPX4 axis and was a positive factor in the prognosis of colon cancer.
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a |
Department of Pathology, Basic Medicine and Forensic Medicine College, North Sichuan Medical College,
Nanchong, Sichuan 637000 China |
b |
Key Lab of Process Analysis and Control of Sichuan Universities, Yibin University, Yibin, Sichuan 644000 China |
* Corresponding author, E-mail: Jianshunhai1972@163.com
Received 13 Apr 2023, Accepted 29 Nov 2023
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