作者
Masako Harada, Juliana Benito, Shinichi Yamamoto, Surinder Kaur, Dirim Arslan, Santiago Ramirez, Rodrigo Jacamo, Leonidas Platanias, Hiromichi Matsushita, Tsutomu Fujimura, Saiko Kazuno, Kensuke Kojima, Yoko Tabe, Marina Konopleva
发表日期
2015/11/11
期刊
Oncotarget
卷号
6
期号
35
页码范围
37930
出版商
Impact Journals, LLC
简介
Mammalian target of rapamycin (mTOR) signaling is a critical pathway in the biology of acute myeloid leukemia (AML). Proviral integration site for moloney murine leukemia virus (PIM) serine/threonine kinase signaling takes part in various pathways exerting tumorigenic properties. We hypothesized that the combination of a PIM kinase inhibitor with an mTOR inhibitor might have complementary growth-inhibitory effects against AML. The simultaneous inhibition of the PIM kinase by pan-PIM inhibitor AZD1208 and of mTOR by selective mTORC1/2 dual inhibitor AZD2014 exerted anticancer properties in AML cell lines and in cells derived from primary AML samples with or without supportive stromal cell co-culture, leading to suppressed proliferation and increased apoptosis. The combination of AZD1208 and AZD2014 rapidly activated AMPKα, a negative regulator of translation machinery through mTORC1/2 …
学术搜索中的文章
M Harada, J Benito, S Yamamoto, S Kaur, D Arslan… - Oncotarget, 2015