Data from Differential Effects of PI3K and Dual PI3K/mTOR Inhibition in Rat Prolactin-Secreting Pituitary Tumors Article Swipe

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Marie Chanal , Pascale Chevallier , Véronique Raverot , Guillaume Fonteneau , K. Lucia , Jose Luis Monteserin Garcia , Alexa Rachwan , Emmanuel Jouanneau , Jacqueline Trouillas , Jérôme Honnorat , Carole Auger , Marily Theodoropoulou , Gérald Raverot ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/1535-7163.c.6537625.v1

Aggressive pituitary tumors are rare but difficult to manage, as there is no effective chemotherapy to restrict their growth and cause their shrinkage. Within these tumors, growth-promoting cascades, like the PI3K/mTOR pathway, appear to be activated. We tested the efficacy of two inhibitors of this pathway, NVP-BKM120 (Buparlisib; pan-PI3K) and NVP-BEZ235 (dual PI3K/mTOR), both in vitro on immortalized pituitary tumor cells (GH3) and on primary cell cultures of human pituitary tumors and in vivo on a rat model of prolactin (PRL) tumors (SMtTW3). In vitro, NVP-BEZ235 had a potent apoptotic and cytostatic effect that was characterized by decreased cyclin D/E and Cdk4/2 protein levels and subsequent accumulation of cells in G₁. In vivo, the effect was transient, with a decrease in mitotic index and increase in apoptosis; long-term treatment had no significant inhibitory effect on tumor growth. In contrast, while NVP-BKM120 had little effect in vitro, it dramatically limited tumor growth in vivo. Increased Akt phosphorylation observed only in the NVP-BEZ235–treated tumors may explain the differential response to the two inhibitors. Primary cell cultures of human PRL pituitary tumors responded to NVP-BEZ235 with reduced cell viability and decreased hormone secretion, whereas NVP-BKM120 had little effect. Altogether, these results show a potential for PI3K inhibitors in the management of aggressive pituitary tumors. Mol Cancer Ther; 15(6); 1261–70. ©2016 AACR.

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PI3K/AKT/mTOR pathway Prolactin In vivo Endocrinology Internal medicine Pituitary tumors Apoptosis Cell growth Cancer research Protein kinase B Biology In vitro Medicine Hormone Biochemistry Biotechnology

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/1535-7163.c.6537625.v1
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DOI: https://doi.org/10.1158/1535-7163.c.6537625.v1

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Title: Data from Differential Effects of PI3K and Dual PI3K/mTOR Inhibition in Rat Prolactin-Secreting Pituitary Tumors

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-04-03

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Authors: Marie Chanal, Pascale Chevallier, Véronique Raverot, Guillaume Fonteneau, K. Lucia, Jose Luis Monteserin Garcia, Alexa Rachwan, Emmanuel Jouanneau, Jacqueline Trouillas, Jérôme Honnorat, Carole Auger, Marily Theodoropoulou, Gérald Raverot

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Concepts: PI3K/AKT/mTOR pathway, Prolactin, In vivo, Endocrinology, Internal medicine, Pituitary tumors, Apoptosis, Cell growth, Cancer research, Protein kinase B, Biology, In vitro, Medicine, Hormone, Biochemistry, Biotechnology

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