Abstract
BackgroundThe 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.MethodsThe 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.ResultsDexmedetomidine 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).ConclusionsDexmedetomidine 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.
Highlights
Surgical excision remains the mainstay of treatment for solid tumors, perioperative immunosuppression may adversely promote residual tumor growth and micrometastasis after surgery [1, 2]
There cortisol levels measured on postoperative day (POD) 3 showed cortisol levels to be significantly lower in the Dexmedetomidine group compared to the Control group (P=0.004)
Blood cytokine levels measured after sacrificing the mice 4 weeks after surgery showed tumor necrosis factor alpha (TNF-a) to be significantly lower in the Dexmedetomidine group compared to the Control group (P
Summary
Surgical excision remains the mainstay of treatment for solid tumors, perioperative immunosuppression may adversely promote residual tumor growth and micrometastasis after surgery [1, 2]. As a potential method to alleviate the surgical stress response (SSR) and reduce immunosuppression, we focused on dexmedetomidine, a highly selective a2 adrenergic agonist well known for its analgesic properties and the ability to suppress SNS activity [7]. An in vivo study found dexmedetomidine to promote metastasis in breast, lung, and colon cancer in rodent models and found it to be dosedependently deleterious [11]. These conflicting results may be due to different cancer types expressing different adrenoreceptors or the use of varying doses of dexmedetomidine. 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
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