HSP90辅侣蛋白P23预测多发性骨髓瘤患者对糖皮质激素的敏感性

Predicating the Sensibility of Patients with Multiple Myeloma to Glucocorticoid by Cochaperone P23

本研究旨在寻找预测多发性骨髓瘤(multiple myeloma,MM)患者对糖皮质激素(glucocorticoid,GC)敏感性的指标。以地塞米松敏感细胞株(MM1.S)、地塞米松抵抗细胞株(MM1.R)、激素敏感和非敏感MM患者10名为研究对象,采用Western blot检测患者外周血单个核细胞(PBMNC)中HSP90和P23蛋白表达,探讨其与GC抵抗的关系。结果表明:HSP90、GR和IκB-α蛋白在MM1.S、MM1.R、正常人和MM患者PBMNC中表达无差异,而P23蛋白表达有明显差异。随着地塞米松浓度增加,MM1.S存活率逐渐下降,而MM1.R下降不明显。P23蛋白低表达患者7例,其中GC联合方案治疗有效者6例(有效率为86%),无效者1例(无效率为14%);P23蛋白高表达患者3例,其中GC联合方案治疗有效者1例(有效率为33%),无效者2例(无效率为67%),二者相比有显著性差异(P<0.05)。结论:P23蛋白表达可以预测MM患者对GC的敏感性,可以此指标指导临床用药。

This study was aimed to investigate the sensitive index for predicting the sensitivity of patients with multiple myeloma （MM） to ghicocorticoid （GC）. MM1. S, MM1. R cell lines and 10 MM patients sensitive or non- sensitive to GC were enrolled in this study. The expression of heat shock protein 90 （HSP90） and P23 in peripheral blood mononuclear cells （PBMNC） of MM patients was detected by Western blot, and its relation with GC resistence was explored. The results showed that there were no differences in HSP90, GR and IKB-~ expressions among MMI. S, MM1. R, PBMNC of normal persons and MM patients, while there was apparent difference in P23; along with increasing of dexamethasone dose, the survival rate of MM1. S decreased, but that of MM1. R did not change so obviously. Among 7 cases with P23 low expression, combination treatment scheme with GC was effective in 6 cases （86%）, uneffective in 1 cases （14%）; while among 3 cases with P23 high expression, 1 cases （33%） showed effective to combination treatment with CJC, 2 cases （67 % ） showed uneffective （ P 〈 0.05 ）. It is concluded that the P23 expression may predict the sensitivity of MM patients to GC and may be used as index for guiding clinical treatment.