New Anti-Cancer Impact of Cerium Oxide, Lithium, and Sn-38 Synergy via DNA Methylation-Mediated Reduction of MMP-2 and Modulation of the PI3K/Akt/mTOR Pathway

氧化铈、锂和Sn-38协同作用通过DNA甲基化介导的MMP-2减少和PI3K/Akt/mTOR通路调节发挥新的抗癌作用

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Abstract

Background/Objectives: Glioblastoma, the most common primary tumor of the central nervous system, is characterized by high malignancy and poor prognosis. One of the main challenges in neurological disorders is to develop an effective treatment modality that can cross the blood-brain barrier. Nanoparticles are revolutionary for neurodegenerative diseases due to their targeted delivery and ability to overcome biological barriers. Cerium oxide (Ce(2)O(3)) nanoparticles are suitable for use as drug delivery systems. Methods: In our study, we investigated the anticancer mechanism using SN-38, lithium, and Ce(2)O(3), a powerful agent used in GBM treatment. We evaluated their anticancer activities separately and in combination with U373 cell lines. GBM cell line U373 cells were cultured. Then, all groups except the control group were treated with different doses of SN-38 and lithium combination therapy with SN-38, lithium, and Ce(2)O(3) combination therapy. The results were evaluated using MTT and ELISA tests. Results: When the results were examined, anticancer activity was detected at PTEN, AKT, mTOR, and BAX/Bcl-2 levels in the SN-38 + NPs 25 µg/mL + Lithium 50 µg/mL and SN-38 + NPs 50 µg/mL + Lithium 50 µg/mL dose groups. In addition, findings that inflammation markers were correlated with the apoptosis mechanism were obtained. Conclusion: This study is the first to report that combining lithium with SN-38 and NPs increased oxidative stress more than lithium with SN-38, leading glioblastoma cells to apoptosis and its potential anticancer activity. These results provide a basis for further investigation of its clinical application in cancer treatment.

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