ABSTRACT
Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA-approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes-associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour-bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti-glioma regimens, thus predicting a broad prospect of clinical application.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Cycle Proteins/metabolism , Imipramine/pharmacology , Intracellular Signaling Peptides and Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Temozolomide/pharmacology , Transcription Factors/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Synergism , Glioma , Humans , Mice , Prognosis , Treatment Outcome , Xenograft Model Antitumor AssaysABSTRACT
Increasing environmental pollution caused by the volatile organic compounds due to their toxicity is a matter of great concern. So it is crucial to develop processes which can destroy these compounds effectively. It has been found that the photocatalytic activity of TiO(2) towards the decomposition of gaseous benzene can be greatly enhanced by loading Pd on the surface of TiO(2). The results show that the optimum palladium loading is 0.25wt.%. The prepared photocatalysts were characterized by XRD, UV-vis diffuse reflectance and XPS. XRD results indicate that no peaks of Pd are detected in the 2theta region from 10 degrees to 90 degrees . Pd/TiO(2) absorbs much more light than TiO(2) in the visible light region. The XPS spectrum shows that there are Ti, O, C and Pd elements on the surface of the Pd/TiO(2), the binding energy values of Ti2p of 0.25%Pd/TiO(2) transfer to a lower value. In addition, the photocatalytic performance of 0.25%Pd/TiO(2) was investigated, the result illustrates that 0.25%Pd/TiO(2) demonstrates 2.32 times the photocatalytic activity of pure TiO(2). The reason of promotion of photocatalytic performance was discussed.
