Dexmedetomidine promotes metastasis in rodent models of breast, lung, and colon cancers

Abstract

The findings call for mechanistic translational studies to understand these deleterious effects of dexmedetomidine, and warrant prospective clinical trials to assess the impact of perioperative dexmedetomidine use on outcomes in cancer patients.

An assessment of the survival impact of multimodal anesthesia/analgesia technique in adults undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched analysis

“…Unlike our study population where patients received propofol in combination with other anesthetics including dexmedetomidine, ketamine, lidocaine, celecoxib, pregabalin and tramadol, patients in the studies by Wigmore et al, and Wu et al received a predominantly propofol-based TIVA without any of the oral and IV adjuncts administered in our MA group. Unlike propofol which has mainly been associated with properties which may reduce the survival of tumors [17][18][19], some of the components of MA in our study namely, dexmedetomidine and ketamine, have been associated with some pro-tumoral effects [20][21][22][23]. For example, dexmedetomidine has been shown to increase tumor cell retention and promote metastasis in rodent models of breast, lung and colon cancers [21].…”

Prognostic significance of α‐ and β2‐adrenoceptor gene expression in breast cancer patients

“…Altogether, these results suggest that the proliferation‐enhancing effect we have described for clonidine and dexmedetomidine, both nonspecific α 2 ‐adrenergic agonists used in clinics in the context of anaesthesia, could be mediated almost exclusively by the α 2C subtype. A recent study has also shown that perioperative use of dexmedetomidine increases the metastatic burden of a mammary adenocarcinoma in rats, Lewis lung carcinoma in C57BL/6 mice, and colon adenocarcinoma in BALB/c mice . Rauwolscine, an α 2 ‐adrenergic antagonist that we proved to be a strong inhibitor of breast tumour growth, has a higher affinity for the α 2C subtype…”

“…A recent study has also shown that perioperative use of dexmedetomidine increases the metastatic burden of a mammary adenocarcinoma in rats, Lewis lung carcinoma in C57BL/6 mice, and colon adenocarcinoma in BALB/c mice. 46 Rauwolscine, an α 2 -adrenergic antagonist that we proved to be a strong inhibitor of breast tumour growth, 15,19,20,44 has a higher affinity for the α 2C subtype. 47 Besides the slight differences in the in vivo physiological actions of α 2A and α 2C -adrenoceptors, 48 until now, no such strong contrast between the 2 had been reported.…”

Effects of dexmedetomidine on glioma cells in the presence or absence of cisplatin

“…Dex is popular not only for its synergistic anaesthetic effect with other anaesthetics, but also for the strong protection against tissue injury and function impairment it provides. Lavon et al 13 found that Dex attenuates stress during surgery and further promotes metastasis of breast, lung and colon cancers in rodent models. 11 α 2 -AR is a G i -type G proteincoupled receptor that reduces intracellular cyclic AMP (cAMP) levels.…”

“…12 However, this protection may be unfavourable for the elimination of a tumour by surgery. Lavon et al 13 found that Dex attenuates stress during surgery and further promotes metastasis of breast, lung and colon cancers in rodent models. An in vitro study also showed that Dex could promote the proliferation, migration and invasion of breast cancer cells through the activation of α 2 -AR/ ERK signalling.…”