Table 2.
Co-treatment strategies aiming at ferroptosis in lung cancer.
| Drug combination | Clinical Application | Target | Effect | Reference | |
|---|---|---|---|---|---|
| Cisplatin + | Propofol | No | GPX4 | Propofol suppresses ferroptosis mediated by GPX4 via the miR-744-5p/miR-615-3p regulatory axis. | (103) |
| Isoorientin | No | SIRT6/Nrf2/GPX4 | Isoorientin enhances ferroptosis while overcoming drug resistance in lung cancer via the SIRT6/Nrf2/GPX4 signaling axis. | (104) | |
| Ginkgetin | No | Nrf2/HO-1, SCL7A11, GPX4 | Ginkgo biloba not only intensified ROS production but also deactivated the Nrf2/HO-1 signaling axis, thereby compromising the REDOX homeostasis in cisplatin-treated cells. Additionally, it amplified cisplatin-triggered MMP loss and apoptosis in NSCLC cells. | (105) | |
| PRLX93936 | No | GPX4 | Cisplatin combined with PRLX93936 can increase ROS, lipid peroxidation and Fe2+ level, inhibit GPX4 and down-regulate NRF2/Keap1 pathway, and reduce cisplatin resistance. | (106) | |
| Gefitinib + | Dihydroisotansh | No | ROS | Dihydroisotansh treatment resulted in significant upregulation of autophagy, accumulation of ROS, and induction of apoptosis and ferroptosis in a dose-dependent manner. | (107) |
| Betulin | No | SCL7A11, GPX4 and FTH1, ROS | Overcoming gefitinib resistance and improving the efficacy of EGFR wild-type/KRAS mutant in NSCLC cells. | (108) | |
| Erastin + | Celastrol | No | ROS, Mitochondria | Co-treatment with low concentrations of erastin and celastrol significantly induced cell death by activating the ROS-mitophagy signaling pathway. | (108) |
| Acetaminophen | No | Nrf2/heme oxygenase-1 | Regulate Nrf2 nuclear translocation, promote the death of NSCLC cells. | (109) | |
| β-Elemene + | erlotinib | No | ROS, GPX4 | Up-regulation of lncRNA H19 induces ferroptosis and enhances the sensitivity of EGFR-TKI resistant lung cancer to erlotinib. | (110) |
| Auranofin + | Olaparib | No | ROS | Killing of mutant p53 NSCLC cells via lipid peroxidation-dependent ferroptosis. | (111) |
| Radiotherapy + | Hemin | No | ROS | Increasing the activity of GPX4 degradation enhances the productivity of initial ROS, leading to lipid peroxidation and ferroptosis. | (112) |
| Erastin | No | GPX4 | Erastin reduces the radiation resistance of NSCLC cells by inhibiting GPX4. | (113) | |
| Rsl3, imidazole ketone erastin | No | _ | Ferroptosis inducers act as radiation sensitizers to enhance the effect of radiation on cytoplasmic lipid peroxidation, leading to cell death. | (114)* | |
* “+” represents the combination.
GPX4, glutathione peroxidase 4; SIRT6, Sirtuin 6; HO-1, Heme oxygenase 1; SLC7A11, solute carrier family 7 member 11; MMP, Matrix metalloproteinase; ROS, reactive oxygen species; KEAP1, kelch like ECH associated protein 1; EGFR, Epidermal growth factor receptor; KRAS, KRAS proto-oncogene; EGFR-TKI, Epidermal growth factor receptor tyrosine kinase inhibitor; FTH1, ferritin heavy chain 1.