S Ciechanowicz1, H Zhao1, Q Chen2, J Cui1, E Mi1, E Mi1, Q Lian3, D Ma4. 1. Department of Surgery and Cancer, Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK. 2. Department of Surgery and Cancer, Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK; Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China. 3. The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, China. 4. Department of Surgery and Cancer, Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK. Electronic address: d.ma@imperial.ac.uk.
Abstract
BACKGROUND: Increasing evidence suggests that perioperative factors including anaesthetics influence cancer recurrence and metastasis after surgery. This study investigated the influence of sevoflurane on the response of lung and renal cancer cells to cisplatin, with focus on transforming growth factor-beta (TGF-β) and osteopontin (OPN) that are both closely associated with cancer tumorigenesis and metastasis. METHODS: Non-small cell lung adenocarcinoma (A549) and renal cell carcinoma (RCC4) cells were exposed to 3.6% sevoflurane for two hrs. Malignant potential represented by cell viability, migration, chemosensitivity to cisplatin was evaluated. Expression of OPN, TGF-β1, TGF-β receptor type II (TGF-βRII) and the canonical downstream effector Smad3 was assessed. SiRNA knockdown of TGF-β1 and OPN and chemical inhibition of TGF-βRI/II was performed. RESULTS: Sevoflurane reduced cell viability (0.394) versus control (0.459) (P < 0.01), enhanced chemosensitivity but had no effect on migration of A549 cells. It enhanced viability (0.467) versus control (0.347) (P < 0.001), chemoresistance and migration of RCC4. In A549, there was enhanced nuclear Smad3. In RCC4, TGF-βRII and OPN were upregulated, while TGF-β1 was over- expressed with reduced nuclear Smad3. TGF-βRII inhibition and OPN knockdown abolished sevoflurane-mediated viability, and migration, respectively, in RCC4. CONCLUSIONS: Sevoflurane promotes the metastatic potential of renal carcinoma, but not of non-small cell lung cancer. This may be associated with its differential effect on cellular signalling including TGF-β. Our findings indicate that sevoflurane may have different effects on the metastatic potential and chemosensitivity of different tumour types.
BACKGROUND: Increasing evidence suggests that perioperative factors including anaesthetics influence cancer recurrence and metastasis after surgery. This study investigated the influence of sevoflurane on the response of lung and renal cancer cells to cisplatin, with focus on transforming growth factor-beta (TGF-β) and osteopontin (OPN) that are both closely associated with cancer tumorigenesis and metastasis. METHODS:Non-small cell lung adenocarcinoma (A549) and renal cell carcinoma (RCC4) cells were exposed to 3.6% sevoflurane for two hrs. Malignant potential represented by cell viability, migration, chemosensitivity to cisplatin was evaluated. Expression of OPN, TGF-β1, TGF-β receptor type II (TGF-βRII) and the canonical downstream effector Smad3 was assessed. SiRNA knockdown of TGF-β1 and OPN and chemical inhibition of TGF-βRI/II was performed. RESULTS:Sevoflurane reduced cell viability (0.394) versus control (0.459) (P < 0.01), enhanced chemosensitivity but had no effect on migration of A549 cells. It enhanced viability (0.467) versus control (0.347) (P < 0.001), chemoresistance and migration of RCC4. In A549, there was enhanced nuclear Smad3. In RCC4, TGF-βRII and OPN were upregulated, while TGF-β1 was over- expressed with reduced nuclear Smad3. TGF-βRII inhibition and OPN knockdown abolished sevoflurane-mediated viability, and migration, respectively, in RCC4. CONCLUSIONS:Sevoflurane promotes the metastatic potential of renal carcinoma, but not of non-small cell lung cancer. This may be associated with its differential effect on cellular signalling including TGF-β. Our findings indicate that sevoflurane may have different effects on the metastatic potential and chemosensitivity of different tumour types.
Authors: Jeremy Watson; Michael K Ninh; Scott Ashford; Elyse M Cornett; Alan David Kaye; Ivan Urits; Omar Viswanath Journal: Oncol Ther Date: 2021-04-16