Research Paper Volume 13, Issue 10 pp 13515—13534

Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin

KIF20A induced NUAK1 activation to up-regulate GPX4 level, thus inducing CRC resistance to Oxaliplatin. (A) The protein-protein interaction between KIF20A and NUAK1 was screened out by String database. (B) WB assay was used to observe whether KIF20A silencing could impact the phosphorylation level of MYPT1S445. Left, HCT116-Or cells. Right, H716 cells. (C, D) The cell (HCT116-Or (C) and H716 (D)) viability was measured to observe whether ETC-1002 would affect the suppression of oxaliplatin on KIF20A-silenced colorectal cancer cells in vitro. The data are presented as the mean ± SD, ***p E) Cell death was assessed by flow cytometry (annexin V-FITC/PI staining) to observe whether ETC-1002 would affect the lethal effect of oxaliplatin on KIF20A-silenced colorectal cancer cells in vitro. Left, representative results of annexin V-FITC/PI staining. Right, quantitative analysis. Top, HCT116-Or cells. Bottom, H716 cells. The data are presented as the mean ± SD, ***p

Figure 3. KIF20A induced NUAK1 activation to up-regulate GPX4 level, thus inducing CRC resistance to Oxaliplatin. (A) The protein-protein interaction between KIF20A and NUAK1 was screened out by String database. (B) WB assay was used to observe whether KIF20A silencing could impact the phosphorylation level of MYPT1S445. Left, HCT116-Or cells. Right, H716 cells. (C, D) The cell (HCT116-Or (C) and H716 (D)) viability was measured to observe whether ETC-1002 would affect the suppression of oxaliplatin on KIF20A-silenced colorectal cancer cells in vitro. The data are presented as the mean ± SD, ***p < 0.001 (versus shKIF20A+Oxaliplatin). (E) Cell death was assessed by flow cytometry (annexin V-FITC/PI staining) to observe whether ETC-1002 would affect the lethal effect of oxaliplatin on KIF20A-silenced colorectal cancer cells in vitro. Left, representative results of annexin V-FITC/PI staining. Right, quantitative analysis. Top, HCT116-Or cells. Bottom, H716 cells. The data are presented as the mean ± SD, ***p < 0.001 (versus shKIF20A+Oxaliplatin).