Fig. 8.

Knock-down of METTL7B reversed the resistance toward TKIs in LUAD cells both in vitro and in vivo. a-c Gold nanocluster-assisted delivery of METTL7B-siRNA was transfected into gefitinib-resistant PC9-GR, H1975 and osimertinib-resistant PC9-OR cells, and the cell viability was evaluated to measure IC₅₀ of TKIs after treatment with different concentrations of gefitinib and osimertinib for 72 h. d-g PC9-GR (d-e) and PC9-OR (f-g) cells were injected into the two flanks of BALB/c nude mice to form subcutaneous tumors. The mice with subcutaneously implanted tumors were treated with TKIs (gefitinib and osimertinib) (30 mg/kg, qd, po) and GNC-siNC or GNC-siMETTL7B as indicated. The growth of tumors was monitored every 3 d. Tumor volume and body weights were presented as mean ± SD from five mice per group. h The schema represented the critical link between METTL7B, GPX4, HMOX1 and SOD1 in TKIs-resistant LUAD cells. **P < 0.01 and ****P < 0.0001