体外沙利度胺抑制骨髓瘤细胞生长及其机制的研究

为了解沙利度胺对初治和复发难治多发性骨髓瘤患者离体瘤细胞生长的影响及其机制 ,用甲基纤维素集落培养法观察不同浓度沙利度胺对初治、复发难治多发性骨髓瘤患者瘤细胞集落形成的影响 ,用IL 6依赖性细胞系和流式细胞术检测 2 0 0 μg/ml沙利度胺作用下骨髓瘤细胞自分泌IL 6和瘤细胞表面IL 6受体的变化。结果表明 ,当沙利度胺浓度分别为 75和 10 0 μg/ml以上时对初治骨髓瘤细胞和复发难治的多发性骨髓瘤细胞集落形成有抑制作用 ,这种抑制作用随着沙利度胺浓度的增加而增强。沙利度胺浓度为 2 0 0 μg/ml时 ,骨髓瘤细胞自分泌IL 6的浓度在初治组和复发难治组分别为 (14 8.5± 96 .7)ng/ml和 (2 86 .2± 189.1)ng/ml,明显低于沙利度胺作用前的水平 (P <0 .0 0 1和 <0 .0 5 )。沙利度胺浓度为 2 0 0 μg/ml时骨髓瘤细胞表面IL 6受体水平在初治组和复发难治组分别为 16 .7%和 2 0 .2 % ,明显低于沙利度胺作用前的水平 (P <0 .0 0 1和 <0 .0 5 )。结论提示 ,沙利度胺不仅对复发难治患者的多发性骨髓瘤细胞体外生长有抑制作用 ,对初治患者也有作用。此外 ,体外沙利度胺可以抑制瘤细胞IL 6分泌和减少瘤细胞表面IL 6受体表达 ,这可能是沙利度胺治疗多发性骨髓瘤有效的机制之一。

In Vitro Inhibition and Mechanism of Multiple Myeloma Cells Growth by Thalidomide

To investigate the influence of the thalidomide on the growth of multiple myeloma cells from untreated, relapsed or refractory patients and summarize its mechanisms, thalidomide influence on colony growth of untreated, relapsed or refractory multiple myeloma cells cultured by semisolid methylcellulose was observed. The level of interleukin-6 (IL-6) autosecreted by myeloma cells was tested by IL-6-dependent cell line when myeloma cells were treated with thalidomide at 200 microgram/ml, and in the same concentration of thalidomide the expression of IL-6 receptor were tested by flow cytometry. Results showed that colony growths of myeloma cell from untreated and relapsed or refractory patients were all colonies were inhibited when treated by thalidomide up to 75 microgram/ml or 100 microgram/ml concentration. The inhibition was concentration-dependent, higher concentration cause more inhibition. After treatment with thalidomide at 200 microgram/ml, the concentrations of IL-6 secreted by myeloma cells were (148.5 +/- 96.7) microgram/ml, and the levels of IL-6 receptor expressed on the cell surface were 16.7% and 20.2% in untreated and relapsed or refractory patients, respectively, and those were significantly lower than those levels in the cells before exposure to thalidomide. It was concluded that thalidomide can inhibit growth of both relapsed or refractory cells and untreated myeloma cells in vitro. Therefore, it can be used to treat untreated multiple myeloma patients. Inhibiting tumor cells secreting level of IL-6 and reducing the expression of IL-6 receptor on myeloma cell surface is one of the mechanisms for thalidomide to remedy multiple myeloma patients