Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) Dox (5 mg/kg) determined the major tumor growth inhibition (-97.29% vs. control) but results in greater toxicity. The combination Rapa Dox (2.5 mg/kg) showed a tumor inhibition like Rapa Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in "poor-responder" GBM patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462908 | PMC |
http://dx.doi.org/10.3390/jcm8030331 | DOI Listing |
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