[Influence of thalidomide on bone marrow microenvironment in refractory and relapsed multiple myeloma].
OBJECTIVE
More and more studies indicated that microenvironment plays a major role in growth, survival, and drug resistance of myeloma cells. Thalidomide is one of agents targeting the bone marrow microenvironment. This study was conducted to investigate the mechanism of thalidomide by observation of influence of thalidomide on bone marrow microenvironment in refractory and relapsed multiple myeloma.


METHODS
The expression of ICAM-1 and VCAM-1 of bone marrow stromal cell (BMSC) membrane of refractory and relapsed multiple myeloma was measured using flow cytometry. The expression of IL-1beta(m)RNA, IL-6mRNA, and TNF-alpha(m)RNA in myeloma BMSC was measured by semiquantitative RT-PCR. The serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor(bFGF) were measured by ELISA.


RESULTS
The average values of fluorescence of ICAM-1 and VCAM-1 on the myeloma BMSC membrane were 13.28+/-4.26 and 10.35+/-2.47, respectively; while the average values of fluorescence after treatment effectively with thalidomide were both lower (4.29+/-0.98 and 3.54+/-0.62) (P< 0.01, P< 0.05). The ratios of IL-1beta(m)RNA, IL-6(m)RNA, and TNF-alpha mRNA to beta-actin of the myeloma BMSC were 1.83+/-0.64, 24.52+/-11.46, and 3.42+/-1.83, respectively; while the ratios after treatment effectively with thalidomide were all lower (0.58+/-0.11, 13.47+/-14.31, and 1.25+/-0.76)(P< 0.05,P< 0.05,P< 0.01). There was no significant difference between the values of ICAM-1 and VCAM-1 or among the ratios of IL-1beta(m)RNA, IL-6(m)RNA, and TNF-amRNA to beta-actin of the myeloma BMSC before and after treatment ineffectively with thalidomide (all P >0.05). The serum levels of VEGF and bFGF of the patients were (150.26+/-19.33) ng/L and (23.78+/-13.63) ng/L, respectively. The serum levels of VEGF and bFGF were higher after treatment (effectively and ineffectively) than those before treatment (P< 0.002, P< 0.005).


CONCLUSIONS
Thalidomide can not only inhibit angiogenesis, but also abrogate the adhesion of multiple myeloma cells to bone marrow stromal cells.
Li
Juan
J
Department of Hematology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou,Guangdong, PRChina. luliyuan@163.net
Luo
Shao-Kai
SK
Hong
Wen-De
WD
Zhou
Zhen-Hai
ZH
Zou
Wai-Yi
WY
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology*; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D018799:Intercellular Adhesion Molecule-1; D013792:Thalidomide