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Effects of dexmedetomidine on A549 non-small cell lung cancer growth in a clinically relevant surgical xenograft model

 Ji Hae Jun  ;  Jae-Kwang Shim  ;  Ju Eun Oh  ;  Kwang-Sub Kim  ;  Young-Lan Kwak  ;  Sarah Soh 
 SCIENTIFIC REPORTS, Vol.13(1) : 12471, 2023-08 
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Animals ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Dexmedetomidine* / pharmacology ; Heterografts ; Humans ; Inflammasomes / metabolism ; Inflammation / pathology ; Interleukin-10 ; Interleukin-18 / metabolism ; Lung Neoplasms* / drug therapy ; Mice ; Mice, Nude ; NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1β and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1β, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1β signaling-induced inflammation and enhancing NK cell activity.

© 2023. The Author(s).
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
Kim, Kwang-Sub(김광섭)
Soh, Sa Rah(소사라) ORCID logo https://orcid.org/0000-0001-5022-4617
Shim, Jae Kwang(심재광) ORCID logo https://orcid.org/0000-0001-9093-9692
Oh, Ju Eun(오주은)
Jun, Ji Hae(전지혜) ORCID logo https://orcid.org/0000-0002-8080-0715
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