■急性淋巴细胞白血病(ALL)是儿童常见的癌症类型。全身麻醉剂通常用于ALL治疗期间经历疼痛手术的患者,但其对ALL恶性肿瘤的影响仍不清楚。在这里,我们的目的是研究异丙酚和七氟醚对迁移的影响,所有细胞的归巢和化学抗性。
■NALM-6和Reh细胞在体外用丙泊酚(5和10μg/ml)或七氟醚(3.6%)处理6小时。然后,收获细胞用于体外粘附测定和迁移测定。在体内实验中,GFP-NALM-6细胞用丙泊酚(10μg/ml)或七氟醚(3.6%)预处理6小时。然后,将细胞静脉注射至C57BL/6雌性小鼠,然后进行活体显微镜检查。对于化学抗性研究,用升高浓度的Ara-c(0.05-50nM)加10μg/ml异丙酚或Ara-C加3.6%七氟醚处理细胞4小时,然后通过CCK-8测定评估细胞活力,并通过流式细胞术检测自噬。
■两种麻醉剂均减少了体内迁移和体内归巢,例如:1)进入骨髓的细胞数量减少,2)归巢位置相对于骨内膜表面的干扰。我们的结果表明,全身麻醉剂降低了表面CXCR4的表达,并且降低了白血病细胞对凝血酶裂解的骨桥蛋白(OPN)的粘附。这些变化可能导致迁移和归位的改变。此外,两种麻醉剂可能通过CXCR4介导的机制使ALL细胞对Ara-c敏感。丙泊酚而不是七氟醚通过诱导细胞毒性自噬增强化疗相关细胞死亡。
■一起,我们的数据表明异丙酚和七氟醚都可以减少所有迁移,并通过CXCR4和OPN介导的机制在体内和体外归巢。两种麻醉剂都可能通过CXCR4介导的机制使ALL细胞对化疗敏感。
UNASSIGNED: Acute lymphoblastic leukaemia (ALL) is a common type of cancer in children. General anaesthetics are often used on patients undergoing painful procedures during ALL treatments but their effects on ALL malignancy remain unknown. Herein, we aim to study the effect of propofol and sevoflurane on the migration,
homing and chemoresistance of ALL cells.
UNASSIGNED: NALM-6 and Reh cells were treated with propofol (5 and 10 μg/ml) or sevoflurane (3.6%) in vitro for six hours. Then, cells were harvested for adhesion assay and migration assay in vitro. In in vivo experiments, GFP-NALM-6 cells were pre-treated with propofol (10 μg/ml) or sevoflurane (3.6%) for six hours. Then, cells were injected intravenously to C57BL/6 female mice followed by intravital microscopy. For chemoresistance study, cells were treated with rising concentrations of Ara-c (0.05-50 nM) plus 10μg/ml of propofol or Ara-C plus 3.6% of sevoflurane for 4 hours, followed by the assessment of cell viability via CCK-8 assay and detection of autophagy via flow cytometry.
UNASSIGNED: Both anaesthetics reduced in vivo migration and in vivo
homing as exemplified by 1) the reduction in the number of cells entering the bone marrow and 2) the disturbance in
homing location in relation to endosteal surface. Our results indicated that general anaesthetics reduced the surface CXCR4 expression and the adhesion of leukaemia cells to thrombin cleaved osteopontin (OPN) was reduced. Those changes might result in the alterations in migration and
homing. In addition, both anaesthetics sensitised ALL cells to Ara-c possibly through CXCR4 mediated mechanisms. Propofol but not sevoflurane enhanced chemo-related cell death via inducing cytotoxic autophagy.
UNASSIGNED: Together, our data suggest that both propofol and sevoflurane could reduce ALL migration, and
homing in vivo and in vitro via CXCR4 and OPN mediated mechanisms. Both anaesthetics could sensitise ALL cells to chemotherapy possibly via CXCR4 mediated mechanisms.