RESUMEN
Methods and Results: The levels of MCF2L were detected by PCR and western blotting assay. The effect of MCF2L on ferroptosis was confirmed by MTT, colony formation assay, Brdu, in vivo animal experiment, and the content of Iron, GSH, ROS, and MDA. The underlying mechanisms were explored by PCR, western blotting, and affinity precipitation assay. Our findings demonstrated that MCF2L is remarkedly upregulated in HCC tissues, and sorafenib can induce the levels of MCF2L, suggesting that MCF2L might function in sorafenib resistance of HCC. Further analysis showed that downregulation of MCF2L enhances HCC cell death induced by sorafenib, and ferroptosis inhibitor can reverse this process. Subsequent experiments showed that downregulation of MCF2L elevates the content of Iron, ROS, and MDA, which are all indicators of ferroptosis. Finally, mechanism analysis showed that MCF2L regulates the PI3K/AKT pathway in a RhoA/Rac1 dependent manner. Conclusions: Our study showed that targeting MCF2L may be a hopeful method to overcome sorafenib-resistance through inducing ferroptosis in HCC.
Asunto(s)
Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Animales , Sorafenib/farmacología , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Regulación hacia Abajo , Especies Reactivas de Oxígeno/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Hierro/metabolismo , Línea Celular TumoralRESUMEN
BACKGROUND: High tibial osteotomy (HTO) is an effective surgical technique that can stop or inhibit the progression of unicompartmental knee osteoarthritis (KOA) to avoid or postpone the need for knee arthroplasty in patients. Whether opening-wedge high tibial osteotomy (OWHTO) is superior to closing-wedge high tibial osteotomy (CWHTO) in treating unicompartmental KOA remains controversial. METHODS: Databases (Cochrane Library, EMBASE, and PubMed) were searched from their establishment to July 1, 2018 for randomized controlled trials comparing the application of OWHTO to CWHTO in patients with unicompartmental KOA. The methodological quality of each included study was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions guideline. Review Manager 5.3.5 software (Cochrane Collaboration, Oxford, UK) was used to synthesize the final results. RESULTS: The results will provide useful information about the effectiveness and safety of OWHTO in patients with unicompartmental KOA. CONCLUSION: The findings of the study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD4201811805.
