Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases.

Abstract

Cholangiocarcinoma (CCA) is a rare but highly aggressive tumor entity for which systemic therapies only showed limited efficacy so far. As OSI-027-a dual kinase inhibitor targeting both mTOR complexes, mTORC1 and mTORC2 - showed improved anti-cancer effects, we sought to evaluate its impact on the migratory and metastatic capacity of CCA cells in vitro. We found that treatment with OSI-027 leads to reduced cell mobility and migration as well as a reduced surviving fraction in colony-forming ability. While neither cell viability nor proliferation rate was affected, OSI-027 decreased the expression of MMP2 and MMP9. Moreover, survival as well as anti-apoptotic signaling was impaired upon the use of OSI-027 as determined by AKT and MAPK blotting. Dual targeting of mTORC1/2 might therefore be a viable option for anti-neoplastic therapy in CCA.

• Authors: Katharina Joechle, Huda Jumaa, Kerstin Thriene, Claus Hellerbrand, Birte Kulemann, Stefan Fichtner-Feigl, Sven A Lang, Jessica Guenzle
• Journal: Frontiers in cell and developmental biology (Front Cell Dev Biol) Vol. 9 Pg. 785979 ( 2021) ISSN: 2296-634X [Print] Switzerland
• PMID: 35096817 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Joechle, Jumaa, Thriene, Hellerbrand, Kulemann, Fichtner-Feigl, Lang and Guenzle.