生长分化因子15在多发性骨髓瘤发病机制中的作用研究进展

Research progress on the role of growth differentiation factor 15 in the pathogenesis of multiple myeloma

随着国内人口老龄化的加剧,多发性骨髓瘤(MM)的发病率、死亡率逐年上升。尽管抑癌药物不断涌现,但肿瘤转移、耐药使MM的治疗仍面临严峻挑战。生长分化因子15(GDF15)与包括β2微球蛋白(β2-MG)在内的多种MM血清标志物相关。GDF15可通过激活Akt/SOX2,并调控microRNA-143-3p/c-MET、Bmi-1/Bim来维持MM细胞的自我更新和增殖。GDF15还可通过参与调节MDR1和Bax/Bcl-2以促进MM耐药,并通过CXCR4/SDF1α促进MM转移,但其作用机制仍有待研究。本文对GDF15在MM各种生理活动中发挥的作用及其机制进行归纳,并对GDF15在MM耐药、转移方面的深入研究进行展望。

With the aggravation of aging in China,the incidence and mortality of multiple myeloma(MM)are increasing year by year.Although anticancer drugs are constantly emerging,the treatment of MM is still facing severe challenges due to tumor metastasis and drug resistance.Clinical studies have shown that growth and differentiation factor 15(GDF15)is associated with a variety of MM serum markers,includingβ2-microglobulin(β2-MG).In addition,in vitro cell studies have confirmed that GDF15 maintains the self-renewing and proliferation of tumor cells by activating Akt/SOX2 and its downstream microRNA-143-3p/c-MET and Bmi-1/Bim.GDF15 is also involved in regulating MDR1 and Bax/Bcl-2 to promote MM drug resistance.Although GDF15 is found to promote MM metastasis,its mechanism of action remains to be elucidated.This review summarizes the role and mechanism of GDF15 in various physiological activities of MM,and the further study of GDF15 on MM resistance and metastasis is expected.