Abstract: Objective To observe the serotonin transporter （SERT） expression in colorectal cancer SW480 cells after treatment with erastin and investigate the effect of regulated SERT expression combined with erastin on ferroptosis in colorectal cancer cells. Methods The colorectal cancer SW480 cells were treated with erastin. CCK8 assay was used to verify cell viability，Western blot was used to evaluate the expression of SERT and ferroptosis related proteins such as SLC7A11，GPX4 and ACSL4，and flow cytometry was used to analyze the levels of ROS in the cancer cells. siRNA interference was used to down ⁃ regulate SERT expression in the SW480 cells and the effect of ferroptotic death in the cancer cells treated with regulated SERT combined with Erastin were observed. Results SW480 cells treated with 10 μmol erastin induced ferroptosis and significantly upregulated SERT expression in the cancer cells. The ferroptotic resistance proteins SLC7A11 and GPX4 in the cancer cells induced by erastin combined with siSERT were significantly reduced，while the ferroptotic executive protein ACSL4 was significantly increased. 5⁃HT stimulation not only reversed the reduction of SLC7A11 and GPX4 and ferroptosis caused by erastin on SW480 cells，but also inhibited the synergistic ferroptotic effect of erastin combined with siSERT. Conclusion Erastin induces ferroptotic cell death in SW480 cells and upregulates SERT expression in a compensatory way. Inhibited SERT can increase ferroptotic sensitivity of colorectal cancer cells to erastin. 

Key words: