内质网应激与多发性骨髓瘤细胞耐药的机制研究

Research progress on the mechanism of endoplasmic reticulum stress and drug resistance in multiple myeloma cells

多发性骨髓瘤是来源于浆细胞的恶性肿瘤,为血液系统第二大常见的恶性肿瘤。以硼替佐米(bortezomib,BTZ)为代表的蛋白酶体抑制剂(proteasome inhibitor,PI)是一类重要的多发性骨髓瘤治疗药物,其总体有效率高达80%-90%。但是,大多数骨髓瘤患者最终会出现耐药,导致疾病复发。因此,增加骨髓瘤细胞对PI的敏感性是一个亟待解决的临床问题。近年来的研究发现,骨髓瘤恶性增殖的过程中,细胞内累积大量异常免疫球蛋白,使内质网(endoplasmic reticulum stress,ER)应激增强,继而激发未折叠蛋白反应(nfolded protein response,UPR)。硼替佐米可阻止蛋白质的降解,增加细胞内的蛋白质负荷,加重ER应激,引发细胞凋亡。文章就ER应激在多发性骨髓瘤中的作用及其与骨髓瘤耐药的关系作一综述,进而为临床治疗多发性骨髓瘤提供新的思路。

Multiple myelomais a malignant tumor derived from plasma cells and is the second most common malignant tumor in the blood system.Proteasome inhibitor(PI),represented by bortezomib(BTZ),is an important class of multiple myeloma treatment drugs,and its overall effective rate is as high as 80%-90%.However,most patients with myeloma will eventually develop drug resistance,leading to recurrence of the disease.Therefore,increasing the sensitivity of myeloma cells to PI is an urgent clinical problem.Recent studies have found that during the process of malignant proliferation of myeloma,the accumulation of a large number of abnormal immunoglobulins in the cells enhances endoplasmic reticulum(ER)stress.ER stress in turn stimulates the unfolded protein response(UPR).Bortezomib can prevent protein degradation,increase protein load in cells,aggravate ER stress,and induce cell apoptosis.This review summarized the role of ER stress in multiple myeloma and the relationship between ER stress and drug resistance of myeloma.