Effect of dexmedetomidine on hypoxia-inducible factor-1alpha signaling pathway during hypoxia in mice with lung cancer / 中华麻醉学杂志

ABSTRACT

Objective@#To evaluate the effect of dexmedetomidine on hypoxia-inducible factor-1alpha (HIF-1 α) signaling pathway during hypoxia in mice with lung cancer.@*Methods@#Eighteen clean-grade healthy adult male BALB/c nude mice, aged 8 weeks, weighing 20-30 g, were divided into 3 groups (n=6 each) using a random number table method: lung cancer group (group L), hypoxia+ lung cancer group (group HL), and hypoxia plus lung cancer plus dexmedetomidine group (group HLD). Human lung adenocarcinoma A549 cell suspension 1×106/150 μl was injected via the tail vein to establish the mouse model of lung cancer.After the model was established successfully, chronic intermittent hypoxia was performed as follows the mice were placed in air-tight modular incubation chambers, and the atmosphere was controlled by a constant gas flow containing 10% O2 for 3 h once a day for 3 weeks.The mice in group HL were exposed to hypoxia.After the end of hypoxia exposure, the animals in group HLD were intraperitoneally injected with dexmedetomidine 25 μg/kg 3 times a week for 3 weeks in total.The mice in group L were placed in air-tight modular incubation chambers and the atmosphere was controlled by a constant gas flow containing 21% O2 for 3 h once a day for 3 weeks, and the equal volume of normal saline was injected intraperitoneally.The mice were sacrificed by cervical dislocation, and the lung tissues were removed for determination of lung cancer nodules count, HIF-1α expression (by immunohistochemistry), expression of HIF-1α, survivin and X chromosome linked inhibitor of apoptosis protein (XIAP) (by Western blot), and expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 (by real-time polymerase chain reaction).@*Results@#Compared with group L, the number of lung cancer nodules was significantly increased, and the expression of HIF-1α, survivin, XIAP, MMP-2 and MMP-9 was up-regulated in the other two groups (P<0.05). Compared with group HL, the number of lung cancer nodules was significantly increased, and the expression of HIF-1α, survivin, XIAP, MMP-2 and MMP-9 was up-regulated in group HLD (P<0.05). A small number of HIF-1α positive cells were found in group L, a medium number of HIF-1α positive cells in group HL, and a large number of HIF-1α positive cells in group HAD.@*Conclusion@#Dexmedetomidine can promote proliferation of tumor cells in mice with lung cancer during hypoxia, and the mechanism is related to activating HIF-1α signaling pathway.