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Antileukaemia effect of rapamycin alone or in combination with daunorubicin on ph+ acute lymphoblastic leukaemia cell line
Author(s) -
Yang Xi,
Lin Juan,
Gong Yuping,
Ma Hongbing,
Shuai Xiao,
Zhou Ruiqing,
Guo Yong,
Shan Qingqing,
He Guangcui
Publication year - 2012
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.1013
Subject(s) - daunorubicin , cancer research , cell culture , chromosomal translocation , medicine , philadelphia chromosome , autophagy , acute lymphocytic leukemia , pharmacology , lymphoblastic leukemia , leukemia , biology , gene , apoptosis , biochemistry , genetics
Abstract The translocation (9;22) (q34;q11), known as the Philadelphia (Ph) chromosome and bcr‐abl fusion gene, is the common cytogenetic abnormality and an unfavourable prognosis in adult acute lymphoblastic leukaemia (ALL). Although chemotherapeutic treatment produced high rates of complete response in approximately 70%–80% of newly diagnosed Ph+ ALL, the onset of resistance and clinical relapse is rapid. Therefore, the efficacy of treatment in Ph+ ALL is still to be determined. In this study, we aimed to assess the antileukemic activity of rapamycin (RAPA) (Sigma‐Aldrich Corporation, MO, USA), a mammalian target of rapamycin inhibitor, alone and in combination with daunorubicin (DNR) (Pharmacia & Upjohn Company, Germany) in a Ph+ acute lymphoblastic cell line SUP‐B15 and a primary Ph+ ALL sample in vitro. Here, we demonstrated that 50 nmol/L of RAPA significantly intensified the inhibition induced by DNR on both Ph+ ALL cell line and a primary Ph+ ALL sample. Notably, we reported that the consequence of DNR treatment induced the over expression of the componets of mammalian target of rapamycin signalling pathway, whereas RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug‐resistant cancer. The synergistic effect was also associated with the increase in autophagy, blockage of cell cycle progression in the G1 phase. Altogether, our results suggest that DNR in combination with RAPA is more effective in the treatment of Ph+ ALL compared with DNR alone. Copyright © 2011 John Wiley & Sons, Ltd.