Mechanisms by which thiazolidinediones induce anti-cancer effects in cancers in digestive organs (Thiazolidinedioneが消化器癌において抗癌作用を誘導する機序)

概要

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著者最終原稿版Increasing evidence have suggested that thiazolidinediones (TZDs) could have a therapeutic potential for patients with cancers. Here, the evidence on the mechanisms by which TZDs could contribute to different steps of cancer biology in the digestive system was summarized. According to studies, TZDs induce anti-cancer actions through 3 main pathways 1) cell growth arrest, 2) induction of apoptosis and 3) inhibition of cell invasion. Cell growth arrest is induced by increased level of p27Kip1. p27Kip1 accumulation is resulted from the inhibition of the ubiqutin-proteasome system and/or inhibition of MEK-ERK signaling. TZDs induce apoptosis through increased levels of apoptotic molecules, such as p53 and PTEN and/or decreased level of anti-apoptotic molecules, such as Bcl-2 and survivin. Inhibition of MEK-ERK signaling-mediated up-regulation of E-cadherin and claudin-4, and/or decreased expression of matrix metalloproteinases (MMPs) such as MMP-2 and MMP-9, play a role in the TZD-induced inhibition of cancer cell invasion. Thus, TZDs are capable of inducing anti-tumor action in a variety of ways in gastrointestinal cancers.
2010-11-01