Pro-apoptotic protein BIM in apoptosis of glucocorticoid-sensitive and -resistant acute lymphoblastic leukemia CEM cells.
Although glucocorticoids (GCs) have been used to treat acute lymphoblast leukemia (ALL) for decades, the mechanisms of GC sensitivity and resistance in ALL cells are poorly understood. This study investigated the role and mechanisms of pro-apoptotic protein BIM in apoptosis of GC-sensitive and- resistant ALL cells. The dramatic apoptosis was observed in GC-sensitive CEM-C7 cells after incubated with DEX for 48 h, while not in GC-resistant CEM-C1 cells. The significant up-regulation of BIM in CEM-C7 cells induced by DEX was also observed, but no up-regulation of BIM was detected in DEX-induced CEM-C1 cells. When treated with DEX plus RU486, a glucocorticoid receptor blocker, the apoptosis and BIM expression of CEM-C7 cells were canceled. P38MAPK-blocking pharmacon SB203580 also significantly inhibited the up-regulation of BIM in CEM-C7 cells. These suggested that the absence of BIM up-regulation is one of the important mechanisms of GC resistance, GC-GR conjugation is indispensible in both GC-induced apoptosis and up-regulation of BIM, and p38 MAPK signal pathway is also involved in this process.
Zhao
Ya-ning
YN
Department of Phymatology, Baoji Municipal Central Hospital, 721008, Shaanxi, Baoji, China.
Guo
Xia
X
Ma
Zhi-gui
ZG
Gu
Ling
L
Ge
Jiao
J
Li
Qiang
Q
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D005938:Glucocorticoids; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases