title: Interleukin-6 and JAK2/STAT3 signaling mediate the reversion of dexamethasone resistance after dexamethasone withdrawal in 7TD1 multiple myeloma cells.
abstract: We previously reported the establishment and characteristics of a DXM-resistant cell line (7TD1-DXM) generated from the IL6-dependent mouse B cell hybridoma, 7TD1 cell line. After withdrawing DXM from 7TD1-DXM cells over 90 days, DXM significantly inhibited the cell growth and induced apoptosis in the cells (7TD1-WD) compared with 7TD1-DXM cells. Additionally, IL-6 reversed while IL-6 antibody and AG490 enhanced the effects of growth inhibition and apoptosis induced by DXM in 7TD1-WD cells. Our study demonstrates that 7TD1-DXM cells become resensitized to DXM after DXM withdrawal, and IL-6 and JAK2/STAT3 pathways may regulate the phenomenon.
authors.affiliation: Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Tuoen
authors.initials: T
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Fei
authors.forename: Kalyan J
authors.initials: KJ
authors.lastname: Gangavarapu
authors.forename: Senyo
authors.initials: S
authors.lastname: Agbenowu
authors.forename: Alok
authors.initials: A
authors.lastname: Bhushan
authors.forename: James C K
authors.initials: JC
authors.lastname: Lai
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Daniels
authors.forename: Shousong
authors.initials: S
authors.lastname: Cao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology* / Q000633:toxicity; D019008:Drug Resistance, Neoplasm; D015850:Interleukin-6 / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D003907:Dexamethasone; D053614:Janus Kinase 2
keywords: AG490; Dexamethasone resistance; Dexamethasone withdrawal; Interleukin-6; JAK2/STAT3 signaling pathway; Multiple myeloma