Combination therapy by targeting METTL17 and ferroptosis suppress CRC tumorigenesis.
A and B. The tumor growth volume, weight, and size of SW620 xenograft tumors were significantly attenuated in the combination group receiving shRNA targeting METTL17 and ML162 treatment compared to monotherapy with either METTL17 knockdown or ML162 treatment. However, the efficacy of the combination treatment was compromised by the administration of Lip-1, a potent ferroptosis inhibitor by blocking lipid peroxidation. Vehicle control, ML162 (10 mg/kg per mouse) and Lip-1 (10 mg/kg per mouse) were intraperitoneally administrated every day starting from day 5 post SW620 inoculation. n = 5 per group.
C and D. H&E, Ki-67, and 4-HNE staining of tissue sections from SW620 xenograft tumors (C). Scale bar = 100 μm. Ki-67-positive tumor cells and 4-HNE signal were quantified at the 400 × field (D), n = 4 per group.
Data are shown as mean ± SD. #p < 0.05, ##p < 0.01, ###p < 0.001 compared to Scramble vehicle group, and ***p < 0.001 compared to indicated two groups, based on two-sided Student's t-test.