Background & 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).
Conclusion: Thalidomide can not only inhibit angiogenesis, but also abrogate the adhesion of multiple myeloma cells to bone marrow stromal cells.