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Rapamycin inhibits the growth of glioblastoma
Antonietta Arcella1, Francesca Biagioni, Maria Antonietta Oliva
1I.R.C.C.S. Neuromed Pozzilli, Italy.
Abstract:
The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume.
Insights
Rapamycin effectively inhibits glioblastoma (GBM) growth in patient-derived cells and xenografts. This mTOR inhibitor significantly reduces tumor volume and doubles survival time in mice, offering potential for GBM treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The molecular target of rapamycin (mTOR) pathway is frequently upregulated in glioblastoma (GBM), correlating with tumor growth, stem cell activity, and recurrence.
- Rapamycin, a potent mTOR inhibitor and autophagy inducer, has shown promise in preclinical GBM studies, but its efficacy in patient-derived cells and in vivo models requires further investigation.
Purpose of the Study:
- To evaluate the efficacy of rapamycin in inhibiting glioblastoma cell growth using both established cell lines and primary patient-derived cells.
- To assess the in vivo therapeutic effects of rapamycin on glioblastoma xenografts in mice, focusing on tumor volume reduction and survival extension.
Main Methods:
- Rapamycin was tested at various doses in vitro on U87Mg glioblastoma cell lines and primary cell cultures from GBM patients.
- The therapeutic potential of rapamycin was evaluated in vivo using nude mouse models with brain xenografts derived from glioblastoma.
Main Results:
- Rapamycin demonstrated significant inhibition of cell growth at doses as low as 10nm in both U87Mg cells and primary GBM cultures.
- In vivo administration of rapamycin in brain xenografts nearly doubled mouse survival time and reduced tumor volume by over 95%.
Conclusions:
- Rapamycin exhibits potent anti-tumor activity against glioblastoma in both in vitro and in vivo models.
- These findings support rapamycin as a potential adjuvant therapy for glioblastoma, warranting further clinical investigation.
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