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Updated: May 14, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
mTORC1 inhibitors suppress meningioma growth in mouse models
Doreen Pachow1, Nadine Andrae, Nadine Kliese
1Department of Neuropathology and Genetics & Molecular Neurobiology, Institute of Biology, Otto-von-Guericke University, Magdeburg, Germany.
Purpose:
To evaluate the mTORC1 (mammalian target of rapamycin complex 1) pathway in meningiomas and to explore mTORC1 as a therapeutic target in meningioma cell lines and mouse models.
Experimental Design:
Tissue microarrays (53 meningiomas of all WHO grades) were stained for phosphorylated polypeptides of mTOR, Akt, and the mTORC1 targets 4EBP1 and p70S6K, the latter being the consensus marker for mTORC1 activity. Expression of proteins and mRNAs was assessed by Western blotting and real-time PCR in 25 tumors. Cell lines Ben-Men-1 (benign), IOMM-Lee and KT21 (malignant), and pairs of merlin-positive or -negative meningioma cells were used to assess sensitivity toward mTORC1 inhibitors in methyl-tetrazolium and bromodeoxyuridine (BrdUrd) assays. The effect of temsirolimus (20 mg/kg daily) on tumor weight or MRI-estimated tumor volume was tested by treatment of eight nude mice (vs. 7 controls) carrying subcutaneous IOMM-Lee xenografts, or of eight (5) mice xenotransplanted intracranially with IOMM-Lee (KT21) cells in comparison to eight (5) untreated controls.
Results:
All components of the mTORC1 pathway were expressed and activated in meningiomas, independent of their WHO grade. A significant dosage-dependent growth inhibition by temsirolimus and everolimus was observed in all cell lines. It was slightly diminished by merlin loss. In the orthotopic and subcutaneous xenograft models, temsirolimus treatment resulted in about 70% growth reduction of tumors (P < 0.01), which was paralleled by reduction of Ki67 mitotic index (P < 0.05) and reduction of mTORC1 activity (p70S6K phosphorylation) within the tumors.
Conclusion:
mTORC1 inhibitors suppress meningioma growth in mouse models, although the present study did not measure survival.
Insights
Targeting the mTORC1 pathway with inhibitors significantly reduced meningioma growth in cell and mouse models. This suggests mTORC1 is a promising therapeutic target for meningioma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Meningiomas are tumors arising from the meninges.
- The mammalian target of rapamycin complex 1 (mTORC1) pathway plays a crucial role in cell growth and proliferation.
- Dysregulation of the mTORC1 pathway is implicated in various cancers.
Purpose of the Study:
- To investigate the activity of the mTORC1 pathway in meningiomas.
- To assess the potential of targeting mTORC1 as a therapeutic strategy for meningioma.
Main Methods:
- Analysis of mTORC1 pathway components in 53 human meningioma tissues.
- Western blotting and real-time PCR to assess protein and mRNA expression.
- In vitro studies using meningioma cell lines treated with mTORC1 inhibitors.
- In vivo studies using mouse xenograft models treated with temsirolimus.
Main Results:
- The mTORC1 pathway was found to be active in all meningiomas, irrespective of grade.
- mTORC1 inhibitors (temsirolimus and everolimus) demonstrated dose-dependent inhibition of meningioma cell growth.
- Temsirolimus treatment led to a significant reduction in tumor growth (approximately 70%) in mouse models.
- Reduced tumor growth correlated with decreased cell proliferation and mTORC1 activity.
Conclusions:
- The mTORC1 pathway is activated in meningiomas and represents a viable therapeutic target.
- mTORC1 inhibitors show efficacy in suppressing meningioma growth in preclinical models.
- Further studies are warranted to explore survival outcomes and clinical applications.
