摘要
背景与目的:越来越多的研究表明,骨髓瘤细胞的生长、生存以及耐药的产生与骨髓微环境密切相关。沙利度胺(thalidomide,Thal)是作用于骨髓微环境的药物之一,我们通过观察沙利度胺对难治、复发多发性骨髓瘤(multiplemyeloma,MM)患者骨髓微环境的影响,进一步了解Thal的作用机制。方法:用流式细胞仪检测沙利度胺治疗前后难治、复发的MM患者骨髓基质细胞膜表面的细胞间粘附分子(ICAM-1)和血管细胞粘附分子(VCAM-1)的表达强度,半定量RT-PCR法检测骨髓基质细胞IL-1βmRNA、IL-6mRNA、TNF-αmRNA的表达,采用酶联免疫吸附法(ELISA)测定其血清VEGF、bFGF水平。结果:难治、复发MM患者骨髓基质细胞(BMSC)膜表面ICAM-1、VCAM-1平均荧光强度分别为13.28±4.26、10.35±2.47,用Thal治疗有效的难治、复发MM患者BMSC膜表面ICAM-1、VCAM-1平均荧光强度分别为4.29±0.98、3.54±0.62,明显受抑制(P<0.05)。难治、复发MM患者BMSCIL-1βmRNA、IL-6mRNA、TNF-αmRNA与β-actin的比值分别为1.83±0.64、24.52±11.46、3.42±1.83,用Thal后有效的难治、复发MM患者BMSCIL-1βmRNA、IL-6mRNA、TNF-αmRNA与β-actin的比值分别为0.58±0.11、13.47±14.31、1.25±0.76,明显受抑制(P<0.05)。而治疗无效的难治。
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 1βmRNA, IL 6mRNA, and TNF αmRNA 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 1βmRNA, IL 6mRNA, and TNF α〓mRNA to β 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 1βmRNA, IL 6mRNA, and TNF amRNA to β 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.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第4期346-349,共4页
Chinese Journal of Cancer
