RESUMEN
BACKGROUND: Although Hippo/Yes-associated protein (YAP) signaling plays crucial roles in radiation sensitivity and resistance of multiple kinds of cancers, its role in the radiation sensitivity of glioma cells remains unclear. The present study aimed to reveal Hippo/YAP role in the radiation sensitivity of glioma cells. METHODS: Glioma U251 cells were administrated with different doses of irradiation. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were used to assess cell viability and apoptosis. Co-immunoprecipitation (co-IP) assay was used to assess the interactions between proteins. RESULTS: The results showed that irradiation exposure significantly inhibited cell viability and induced cell apoptosis in a dose-dependent manner, as well as decreased YAP1 expression via enhancing RCHY1-mediated YAP1 protein degradation. In addition, we observed that downregulation of YAP1 or RCHY1 weakened the role of irradiation exposure in cell viability inhibition and apoptosis promotion. CONCLUSION: Collectively, this study emphasizes the vital role of Hippo/YAP signaling in radiation sensitivity of glioma, that RCHY1-mediated YAP1 protein downregulation is a main mechanism accounting for radiation-induced glioma cell apoptosis. Our study may enrich the theoretical basis of Hippo/YAP signaling as a new target for improving radiation sensitivity in glioma.
RESUMEN
Multifunctional theranostic agents are widely applied in cancer diagnosis and treatment. These agents can significantly improve therapeutic outcomes and reduce adverse effects in current cancer therapy. Here, we have designed and synthesized iron-doped copper sulfide nanoparticles with polyvinylpyrollidone (FCS@PVP NPs) for magnetic resonance imaging (MRI) guided photothermal therapy. The biocompatible FCS@PVP NPs with strong near-infrared absorption could be used as the photothermal agent and the magnetic characteristic of Fe3+ ions could be applied to T 1-weighted magnetic resonance imaging (MRI). The T 1-weighted MRI, high photothermal performance, and the biodistribution of FCS@PVP NPs were investigated in mice after intravenous administration. The data showed that there was a high accumulation of FCS@PVP NPs in the tumor sites because of the enhanced permeability and retention (EPR) effect. This result also indicated that the tumors in tumor-bearing mice were effectively suppressed after FCS@PVP NPs treatment under 808 nm laser irradiation. More importantly, FCS@PVP NPs show low cytotoxicity and few side effects because of the quick and safe elimination through the hepatobiliary/fecal route. This work provided a foundation for the clinical application of FCS@PVP NPs as a promising multifunctional theranostic agent for the MRI guided photothermal therapy of cancer.