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Immunomodulatory Effects of Perioperative Dexmedetomidine in Ovarian Cancer: An In Vitro and Xenograft Mouse Model Study

Authors
 Seokyung Shin  ;  Ki Jun Kim  ;  Hye Jeong Hwang  ;  Sewon Noh  ;  Ju Eun Oh  ;  Young-Chul Yoo 
Citation
 FRONTIERS IN ONCOLOGY, Vol.11 : 722743, 2021-10 
Journal Title
FRONTIERS IN ONCOLOGY
Issue Date
2021-10
Keywords
dexmedetomidine ; immunomodulation ; ovarian cancer ; surgical stress response ; sympathetic nervous system
Abstract
Background: The surgical stress response (SSR) causes immunosuppression which may cause residual tumor growth and micrometastasis after cancer surgery. We investigated whether dexmedetomidine affects cancer cell behavior and immune function in an ovarian cancer xenograft mouse model.

Methods: The effect of dexmedetomidine on cell viability and cell cycle was assessed using SK-OV-3 cells at drug concentrations of 0.5, 0.1, 5, and 10 µg mL-1. BALB/c nude mice were used for the ovarian cancer model with the Dexmedetomidine group (n=6) undergoing surgery with dexmedetomidine infusion and the Control group (n=6) with saline infusion for 4 weeks. Natural killer (NK) cell activity, serum proinflammatory cytokines, and cortisol were measured at predetermined time points and tumor burden was assessed 4 weeks after surgery.

Results: Dexmedetomidine had no effect on cell viability or cell cycle. Following a sharp decrease on postoperative day (POD) 1, NK cell activity recovered faster in the Dexmedetomidine group with significant difference vs. the Control group on POD 3 (P=0.028). In the Dexmedetomidine group, cortisol levels were lower on POD 3 (P=0.004) and TNF-α levels were lower at 4 weeks after surgery (P<0.001) compared to the Control group. The Dexmedetomidine group showed lower tumor burden at 4 weeks vs. the Control group as observed by both tumor weight (P<0.001) and the in vivo imaging system (P=0.03).

Conclusions: Dexmedetomidine infusion may improve ovarian cancer surgery outcome by suppressing the SSR and stress mediator release. Further studies are needed to elucidate the mechanisms by which dexmedetomidine acts on cancer and immune cells.
Files in This Item:
T202105078.pdf Download
DOI
10.3389/fonc.2021.722743
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ki Jun(김기준) ORCID logo https://orcid.org/0000-0003-1950-7998
Shin, Seokyung(신서경) ORCID logo https://orcid.org/0000-0002-2641-0070
Oh, Ju Eun(오주은)
Yoo, Young Chul(유영철) ORCID logo https://orcid.org/0000-0002-6334-7541
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187126
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