Molecular mechanisms and impact of anaesthetics on cancer cell biology
File(s)
Author(s)
Datoo, Tanweer
Type
Thesis
Abstract
Surgery remains the first-line treatment for patients with localised solid tumours. However, despite the intent to be curative, by removing or reducing the tumour mass, surgery inadvertently opens a window of opportunity for metastatic outbreak that can be fatal. The perioperative period is considered to be a critical phase in influencing long-term cancer outcomes. Anaesthetic agents and/or techniques used during surgery have been suggested to influence postoperative metastatic spread by directly interfering with cancer cell biology, but research remains limited in this area. In this project, the impacts of the volatile inhalational anaesthetic sevoflurane and the intravenous anaesthetic propofol, both used for induction and maintenance of general anaesthesia, were investigated on ovarian cancer cells in vitro. In addition, the effects of two widely used sedatives, dexmedetomidine and midazolam, were investigated on neuroglioma and lung cancer cells in vitro and in a xenograft model of lung carcinoma. The data show that sevoflurane and dexmedetomidine enhanced the metastatic potential of cancer cells, as observed by increased proliferation and migration. Sevoflurane modulated the hypoxia signalling pathway, while dexmedetomidine exerted its effects largely through α2-adrenoceptor activation. Conversely, propofol and midazolam were found to possess anti-cancer properties, particularly through the induction of cancer cell death. Furthermore, midazolam substantially decreased tumour growth in the xenograft model. The data presented in this thesis has important clinical implications, suggesting caution in the use of sevoflurane and dexmedetomidine during the perioperative period, but encouraging the administration of propofol and midazolam, although further studies, in particular clinical trials, are urgently needed. This thesis expands the field of research into anaesthetics and cancer cell biology significantly, likely contributing to the foundation required for further in vivo work and clinical trials to be carried out in order to identify the most appropriate anaesthetic regime(s) to maximise patient survival after cancer surgery.
Version
Open Access
Date Issued
2018-10
Date Awarded
2019-03
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Ma, Daqing
Bevan, Charlotte
Sponsor
Imperial College London
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)