Effect of vincristine, adriamycin and glucocorticoids on myeloma cells in vitro.
The effect of in vitro exposure to vincristine, Adriamycin, and glucocorticoids was studied in 4 human myeloma cell lines. The drug concentrations tested approximated the steady-state plasma level achievable clinically. Marked growth inhibition was seen in all 4 cell lines with vincristine, but in only 2 with Adriamycin. Glucocorticoids were only minimally inhibitory. The inhibition by glucocorticoids was reversible after drug removal, but that by vincristine and Adriamycin was sustained except the vincristine inhibition of ARH-77 cells. The degree of cell growth inhibition paralleled the reduction in tumor cell 3H-thymidine uptake. Cell cycle distribution analysis showed an arrest of myeloma cells at M/G2 phase by vincristine and Adriamycin and an inhibition of myeloma cells from entering into S phase by dexamethasone. Dose-response analysis with ARH-77 cells, a cell line that appeared the most chemoresistant, showed that the growth-inhibitory effect of Adriamycin and vincristine was roughly proportional to the product of drug concentration and exposure time. However, in contrast to Adriamycin, an effective vincristine concentration and exposure time that totally inhibited cell growth was unable to prevent cell regrowth after drug removal. A higher vincristine concentration appeared to be more effective in preventing cell regrowth.
Department of Medicine, University of Illinois College of Medicine, Chicago 60612.
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YH
Chen
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Feng
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Schilder
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002452:Cell Count / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014750:Vincristine / Q000008:administration & dosage*
D005938:Glucocorticoids; D014750:Vincristine; D004317:Doxorubicin