该研究探讨了Stathmin1 (STMN1)在多发性骨髓瘤 (MM) 中与药物耐药和细胞增殖的生物学功能以及其相关机制。从20名MM患者的骨髓穿刺液中收集骨髓单个核细胞 (BMMCs)，经Ficoll-Hypaque密度梯度离心分离。收集20名单克隆未定性小蛋白血症 (MGUS) 患者和20名健康献血者的血样。将从MGUS患者和健康人的外周血中分离的正常浆细胞作为对照。建立了两种波替单抗 (BTZ) 耐药的MM细胞系，即NCI-H929/BTZ和KM3/BTZ细胞，然后转染携带sh-STMN1的潜伏病毒，以降低BTZ耐药细胞中的STMN1水平。通过RT-qPCR和Western blotting检测STMN1的表达。通过CCK-8实验评价50%生长抑制 (IC50) 值。通过荧光显微镜观察转染潜伏病毒的BTZ耐药细胞中的绿色荧光蛋白。通过MTT实验、集落形成实验、流式细胞术分析和TUNEL染色评估细胞的存活能力、增殖、细胞周期和凋亡。STMN1在MM细胞和MM患者的骨髓穿刺液中上调。此外，STMN1的沉默减轻了MM细胞对BTZ的耐药性。此外，STMN1的下调限制了BTZ耐药细胞的恶性表型。从机制上讲，STMN1的下调在BTZ耐药细胞中使PI3K/Akt信号通路失活。STMN1沉默通过抑制PI3K/Akt信号传导抑制了MM中的细胞增殖和BTZ耐药。

This study investigates the biological functions of Stathmin1 (STMN1) involving drug resistance and cell proliferation in multiple myeloma (MM) and its related mechanisms.Bone marrow aspirates were collected from 20 MM patients, and the bone marrow mononuclear cells (BMMCs) were separated by Ficoll-Hypaque density gradient centrifugation. Blood samples of 20 patients with monoclonal gammopathy of undetermined significance (MGUS) and 20 healthy donors were collected. Normal plasma cells sorted from the peripheral blood of MGUS patients and healthy subjected as controls. Two bortezomib (BTZ)-resistant MM cell lines were established, namely NCI-H929/BTZ and KM3/BTZ cells, and then transfected with lentiviruses packaging sh-STMN1 to knock down STMN1 level in BTZ-resistant cells. Expression of STMN1 was assessed by RT-qPCR and western blotting. CCK-8 assays were performed to assess 50% growth inhibition (IC50) values. Green fluorescent protein in BTZ-resistant cells infected with lentiviruses was observed by fluorescence microscopy. Cell viability, proliferation, cell cycle, and apoptosis were evaluated through MTT assays, colony formation assays, flow cytometry analyses, and TUNEL staining.STMN1 was upregulated in MM cells and bone marrow aspirates of MM patients. Additionally, STMN1 depletion attenuated BTZ resistance in MM cells. Moreover, downregulation of STMN1 limited the malignant phenotypes of BTZ-resistant cells. Mechanistically, the PI3K/Akt signaling was inactivated by STMN1 downregulation in BTZ-resistant cells.STMN1 silencing inhibits cell proliferation and BTZ resistance in MM by inactivating the PI3K/Akt signaling.