Telmisartan Inhibits Non-Small Cell Lung Cancer by Inducing Ferroptosis through the NRF2/GPX4 Signaling Axis.

[INTRODUCTION] Non-Small Cell Lung Cancer (NSCLC) treatment is often challenged by drug resistance. The antihypertensive drug telmisartan has shown anti-tumor potential, but its underlying mechanism remains unclear. Ferroptosis, a newly identified form of cell death, may serve as a promising therapeutic target. The objective is to investigate whether telmisartan inhibits NSCLC by inducing ferroptosis and to elucidate its underlying mechanism.

[METHODS] in vitro cell assays and in vivo mouse models were used, along with molecular biology techniques, to evaluate the effects of telmisartan on NSCLC and its mechanism of action.

[RESULTS] Telmisartan significantly suppressed NSCLC cell proliferation and tumor growth. Mechanistic studies revealed that telmisartan induced ferroptosis by inhibiting the nuclear translocation of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) and downregulating Glutathione Peroxidase 4 (GPX4) expression. The anti-tumor effect of telmisartan was reversed by ferroptosis inhibitors.

[DISCUSSION] Telmisartan can inhibit the proliferation of NSCLC cells in vitro and in vivo and induce cell ferroptosis. Telmisartan can also inhibit the nuclear translocation of NRF2, thereby affecting the expression of GPX4.

[CONCLUSION] Telmisartan inhibited NSCLC by inducing ferroptosis via the NRF2/GPX4 axis, offering a new therapeutic strategy and potential clinical application for NSCLC treatment.