[Bortezomib-induced BiP expression and apoptosis in multiple myeloma cells].
This study was aimed to explore the effect of bortezomib on the apoptosis and expression of the molecular chaperone BiP in human multiple myeloma cell line NCI-H929 (H929). After treatment of H929 cells with different concentrations of bortezomib for 24 hours, cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining, and the expression levels of BiP mRNA and protein were detected by RT-PCR and Western blotting analysis. The results showed that bortezomib of different concentrations (20, 40 and 80 nmol/L) induced apoptosis of H929 cells in dose-dependent manner, with apoptotic rates (15.73 +/- 0.67)%, (27.83 +/- 1.26)% and (44.17 +/- 2.25)% respectively, which were significantly higher than that in control (1.21 +/- 0.07%) (p < 0.05). Bortezomib-induced up-regulation of BiP mRNA levels was almost on a parallel with BiP protein when compared with control. Under the similar apoptosis-stimulating conditions with apoptotic rates varying from 40% to 50%, expression levels of BiP mRNA and BiP protein induced by the classical endoplasmic reticulum stressor Brefeldin A (500 ng/ml, 24 h) were almost consistent with those by bortezomib (80 nmol/L, 24 h). It is concluded that bortezomib-induced apoptosis in H929 cells correlates closely with endoplasmic reticulum stress.
Dong
Hong-Juan
HJ
Department of Hematology, The Fourth Military Medical University, Xi'an 710032, China.
Chen
Xie-Qun
XQ
Gao
Guang-Xun
GX
Gu
Hong-Tao
HT
Pan
Yao-Zhu
YZ
Gao
Ying
Y
Zhu
Hua-Feng
HF
D017209:Apoptosis / Q000187:drug effects*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics
D001897:Boronic Acids; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D011719:Pyrazines; D012333:RNA, Messenger; D000069286:Bortezomib