title: Autophagy in drug resistance of the multiple myeloma cell line RPMI8226 to doxorubicin.
abstract: We investigated the effect of autophagy on drug resistance of multiple myeloma (MM) to doxorubicin (DOX). A DOX-resistant MM cell line (RPMI8226/DOX) was developed by progressively increasing the DOX concentration gradient. The drug resistance index was determined using the MTT method. Transmission electron microscopy, anti-light chain 3-fluorescein isothiocyanate immunofluorescence, and Western blotting were used to detect autophagy of MM cells. Flow cytometry was applied to detect changes in apoptosis of RPMI8226/DOX cells (stained with annexin-V/propidium iodide) caused by inhibition by hydroxychloroquine and 3-methyladenine on autophagy. The drug resistance index of RPMI8226/DOX to DOX was 10.8, and autophagy/lysosomal was clearly observed in RPMI8226/DOX cells under transmission electron microscopy, while immunofluorescence showed granular immunofluorescence in cells. Western blot analysis showed that light chain 3-II protein expression level was higher in RPMI8226/DOX cells than in RPMI8226/S cells. The apoptosis test showed that hydroxychloroquine or 3-methyladenine partially reversed the drug resistance of RPMI8226/DOX cells by inhibiting autophagy. Activation of autophagy in MM cells may explain the drug resistance of myeloma.
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Pan
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: H
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: C-B
authors.initials: CB
authors.lastname: Wang
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Lanzhou General Hospital, Lanzhou,Gansu Province, China.
authors.forename: R
authors.initials: R
authors.lastname: Xi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D004317:Doxorubicin