Volume 49 Number 3

Role and mechanism of FDFT1 in regulating ferroptosis in colon cancer cells via the Nrf2/GPX4 pathway

Lin Mo^a, Xiaolin Wang^a, Xin Liu^a, Jian Gao^a, Chao Tan^b, Shunhai Jian^a,*

 
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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* Corresponding author, E-mail: Jianshunhai1972@163.com

Received 13 Apr 2023, Accepted 29 Nov 2023