Authors: Yinghui Song Meizuo Zhong Pingping Gan Pingyong Yi Youhong Tang Yiping Liu Jinqiong Jiang Li Li
Publish Date: 2014/10/25
Volume: 35, Issue: 12, Pages: 11809-11817
Abstract
Although there have been substantial advances in our knowledge of the resistance of diffuse large B cell lymphoma DLBCL to chemotherapy there are few efficient treatment strategies for recurrent/refractory DLBCL The aim of this study was to investigate the role of aldehyde dehydrogenase ALDH 1A1 in the resistance of diffuse large B cell lymphoma to the chemotherapeutic mixture consisting of cyclophosphamide doxorubicin vincristine and prednisone CHOP The involvement of ALDH1A1 in DLBCL was elucidated by knockdown and pharmacologic inhibition Cell Counting Kit8 CCK8 and clone formation assays were used to determine its role in CHOP sensitivity and clone formation ability Caspase colorimetric assay was used to measure the extent of apoptosis Western blot analysis was used to measure signal transducer and activator of transcription 3 STAT3/nuclear factor kappa B NFκB signaling proteins and quantitative realtime PCR RTPCR was used to measure the differential expression of ALDH1A1 of DLBCL patients and healthy donors ALDH1A1 showed a 564fold higher expression in malignant B cells than in normal B cells Diethylaminobenzaldehyde DEAB decreased the half maximal inhibitory concentration IC50 of the CHOP regimen in Farage cells from 34478 ± 6575 to 18388 ± 4975 ng/ml P = 0004 Both knockdown and inhibition of ALDH1A1 reduced clonogenicity increased caspase3/caspase9 activity and attenuated the phosphorylation status of STAT3/NFκB The prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels of expression P = 0044 ALDH1A1 is a new mediator for resistance of DLBCL to CHOP it is a predictor of clinical prognosis and may serve as a potential target to improve chemotherapy responsiveness of human DLBCL
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