c-Met和微管蛋白抑制剂Tivantinib（ARQ197）及在间皮瘤细胞中的培美曲塞的协同作用

Title:Synergistic Activity of the c-Met and Tubulin Inhibitor Tivantinib (ARQ197) with Pemetrexed in Mesothelioma Cells

Volume: 15 Issue: 14

Author(s): Leticia G. Leon, Maria Gemelli, Rocco Sciarrillo, Amir Avan, Niccola Funel and Elisa Giovannetti

Affiliation:

关键词: c-Met，恶性胸膜间皮瘤，转移，培美曲塞，协同交互作用，tivantinib，微管蛋白

摘要: Malignant pleural mesothelioma (MPM) is a lethal disease with scarce therapeutic options, and preclinical studies on new targeted-agents are warranted. Because previous studies reported high c-Met expression and alterations in the microtubules network in most MPM samples, we evaluated the activity of tivantinib, which has been recently suggested to affect microtubule polymerization in addition to inhibiting c-Met. In four MPM cell lines tivantinib inhibited both c-Met activity and microtubule polymerization, resulting in inhibition of cell-growth with IC₅₀s ranging between 0.3 µM (MSTO-211H) and 2.4 µM (H2052). Furthermore tivantinib synergistically enhanced the antiproliferative and proapoptotic activity of pemetrexed, as detected by sulforhodamine-B-assay and flow cytometry. The synergistic interaction was associated with reduction of thymidylate synthase expression and inhibition of migratory activity. In aggregate, these data show the ability of tivantinib to specifically target key pathways in MPM cells and synergistically interact with pemetrexed, supporting further studies on this therapeutic approach.

Cite this article as:

Leticia G. Leon, Maria Gemelli, Rocco Sciarrillo, Amir Avan, Niccola Funel and Elisa Giovannetti , Synergistic Activity of the c-Met and Tubulin Inhibitor Tivantinib (ARQ197) with Pemetrexed in Mesothelioma Cells, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/1389450116666141205160924