IL-6 is a key factor in growth inhibition of human myeloma cells induced by pravastatin, an HMG-CoA reductase inhibitor.
Although recent developments in initial chemotherapeutic regimens and stem cell transplantation have achieved improvements of initial remission for myeloma patients, relapse and recurrence are still major problems. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been developed for treating hyperlipidemia. Recently, there have been several reports concerning the effects of statins on cancer cells including liver, colon, leukemia, malignant B, stomach, and breast cells. In this study, the in vitro effects of pravastatin on human myeloma cells and the factors closely related to its growth inhibitory effects were examined. Although concentrations were higher than those used clinically, 4 out of 10 myeloma lines showed growth inhibition by pravastatin. The study of factors related to the inhibition indicated IL-6 is important. Indeed, rhIL-6 abolished pravastatin-induced growth inhibition in KMS-21BM cells which did not express IL-6. Statins may be useful in maintenance therapy for myeloma after the screening of IL-6 status.
Otsuki
Takemi
T
Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan. takemi@med.kawasaki-m.ac.jp
Sakaguchi
Haruko
H
Eto
Masaaki
M
Fujii
Tomohiro
T
Hatayama
Tamayo
T
Takata
Akiko
A
Tsujioka
Takayuki
T
Sugihara
Takashi
T
Hyodoh
Fuminori
F
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D017035:Pravastatin / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014867:Water / Q000737:chemistry
D004396:Coloring Agents; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D014867:Water; D012313:RNA; D006903:Hydroxymethylglutaryl CoA Reductases; D001973:Bromodeoxyuridine; D017035:Pravastatin