职业与健康 ›› 2025, Vol. 41 ›› Issue (7): 904-910.

• 论著 • 上一篇    下一篇

职业性镉暴露对白血病细胞株HL-60恶性生物学行为及circRNA-SMAD7、Tspan15表达的影响

阳进   

  1. 眉山市人民医院儿科,四川 眉山 620010
  • 收稿日期:2024-06-16 修回日期:2024-07-02 出版日期:2025-04-01 发布日期:2025-12-17
  • 作者简介:阳进,女,副主任医师,主要从事儿童白血病的治疗研究工作。
  • 基金资助:
    眉山市科技计划项目(2023047)

Effects of occupational cadmium exposure on malignant biological behavior of leukemia cell line HL-60 and expression of circRNA-SMAD7 and Tspan15

YANG Jin   

  1. Department of Pediatrics,People's Hospital of Meishan City,Meishan,Sichuan 620010,China
  • Received:2024-06-16 Revised:2024-07-02 Online:2025-04-01 Published:2025-12-17

摘要: 目的 探讨职业性镉暴露对白血病细胞株HL-60恶性生物学行为及环状 RNA-SMAD7(circular RNA-SMAD7,circ-SMAD7)、四跨膜蛋白15(tetraspanin15,Tspan15)表达的影响。方法 将对数生长期的白血病细胞株HL-60分别暴露于为0、250、500、1 000 nmol/L的氯化镉溶液培养72 h,MTT试剂盒、结晶紫染色测定细胞活性及细胞集落水平,流式细胞仪测定细胞周期及细胞凋亡水平,Transwell及划痕实验测定细胞侵袭迁移水平,RT-PCR法及蛋白印记法测定细胞circRNA-SMAD7及Tspan15水平。结果 与白血病细胞株HL-60组比较,氯化镉低、中、高剂量组的存活率、单克隆形成数目、穿膜数、迁移距离升高,凋亡率、细胞周期G2/M期、circRNA-SMAD7水平(6.39±0.63 vs 4.88±0.43、3.23±0.35、1.89±0.17)降低(P<0.05),Tspan15mRNA蛋白水平(1.15±0.10 vs 2.31±0.21、3.25±0.33、4.80±0.41;0.26±0.05 vs 0.52±0.10、0.82±0.15、1.59±0.23)升高(P<0.05);随着氯化镉加量的增加各氯化镉剂量组存活率、单克隆形成数目、穿膜数、迁移距离逐渐升高,凋亡率、细胞周期G2/M期、circRNA-SMAD7水平逐渐降低,Tspan15mRNA蛋白水平逐渐升高,差异均有统计学意义(均P<0.05)。结论 镉能促进白血病细胞株HL-60增殖、侵袭,抑制凋亡,诱导细胞周期阻滞,其机制可能与镉抑制白血病细胞株HL-60 circ-SMAD7水平,进而靶向上调Tspan15表达有关。

关键词: 镉, 白血病, 恶性生物学行为, circRNA-SMAD7, Tspan15

Abstract: Objective To explore the effects of occupational cadmium exposure on the malignant biological behavior of leukemia cell line HL-60 and the expression of circular RNA-SMAD7(circ-SMAD7) and tetraspanin15(Tspan15). Methods The leukemia cell line HL-60 in the logarithmic growth phase was exposed to 0,250,500,and 1 000 nmol/L cadmium chloride solutions for 72 hours. MTT kit and crystal violet staining were used to measure cell viability and cell colony level. The flow cytometry was used to measure cell cycle and apoptosis level. Transwell and scratch experiments were used to measure cell invasion and migration level. RT-PCR and Western blot methods were used to measure cellular circRNA-SMAD7 and Tspan15 level. Results Compared with the leukemia cell line HL-60 group,the survival rate,number of monoclonal formation,number of membrane penetrations,and migration distance of the low-,medium-,and high-dose cadmium chloride groups were increased,and the apoptosis rate,cell cycle G2/M phase,and the level of circRNA-SMAD7(6.39±0.63 vs 4.88±0.43,3.23±0.35,1.89±0.17) decreased(P<0.05),while the level of Tspan15 mRNA protein(1.15±0.10 vs 2.31±0.21,3.25±0.33,4.80±0.41,0.26±0.05 vs 0.52±0.10,0.82±0.15,1.59±0.23) increased(P<0.05). With the increase in the amount of cadmium chloride,the survival rate,the number of monoclonal formation,the number of membrane penetration and migration distance gradually increased in cadmium chloride groups,and the apoptosis rate,cell cycle G2/M phase,and the level of circRNA-SMAD7 gradually decreased,while the level of Tspan15mRNA protein gradually increased,and the differences were all statistically significant(all P<0.05). Conclusion The cadmium can promote the proliferation and invasion of leukemia cell line HL-60,inhibit apoptosis,induce cell cycle arrest,and its mechanism may be related to the fact that cadmium inhibits the level of leukemia cell line HL-60 circ-SMAD7,thereby targeting up-regulation of Tspan15 expression.

Key words: Cadmium, Leukemia, Malignant biological behavior, circRNA-SMAD7, Tspan15

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