Upregulated Expression of BCL-2 in Multiple Myeloma Cells Induced by Exposure to Doxorubicin, Etoposide, and Hydrogen Peroxide

摘要: Enhanced expression of the antiapoptotic gene BCL-2 may participate in chemoresistance. To ascertain if multiple myeloma cells surviving exposure to chemotherapy alter their expression, we treated cell lines 8226, IM-9, and U266 as well a primary culture with various injurious agents. Doxorubicin, etoposide, hydrogen peroxide consistently induced concentration- time-dependent upregulation all target types assayed by flow cytometry Western blot analysis. In contrast, serum starvation, dexamethasone, anti-fas antibodies had no effect on expression. was relatively selective treatments Ig light chains, BCL-X, or actin. An reverse transcriptase-polymerase chain reaction assay showed increased levels RNA 8226 early 4 hours after treatment doxorubicin at time when recoveries were not decreased. Thus, stimulates individual rather than simply allowing selected survival high BCL-2-expressing culture. Doxorubicin-treated upregulated resistant second doxorubicin. addition, BCL-2-transfected IM-9 cells, enhanced which comparable that achieved initial doxorubicin, etoposide cytotoxicity. These data suggest chemotherapeutic agents enhance contribute acquired