Effect of dexmedetomidine on hypoxia-inducible factor-1alpha signaling pathway during hypoxia in mice with lung cancer
10.3760/cma.j.issn.0254-1416.2019.09.027
- VernacularTitle: 右美托咪定对肺癌小鼠低氧时HIF-1α信号通路的影响
- Author:
Tao ZHANG
1
;
Feng XU
;
Mingli GAO
;
Hua LIANG
;
Hong WANG
;
Jiying ZHONG
;
Hanbing WANG
Author Information
1. Department of Anesthesiology, the First People′s Hospital of Foshan, Foshan 528000, China
- Publication Type:Journal Article
- Keywords:
Dexmedetomidine;
Lung neoplasms;
Hypoxia-inducible factor 1, alpha subunit
- From:
Chinese Journal of Anesthesiology
2019;39(9):1132-1134
- CountryChina
- Language:Chinese
-
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.
